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  • 1. World Journal of Nuclear Medicine Volume 4, Supplement 1, October 2005 INTERNATIONAL CONFERENCE ON RADIOPHARMACEUTICAL THERAPY (ICRT-2005) Limassol, Cyprus 11-14 October 2005 WORLD FEDERATION OF NUCLEAR MEDICINE AND BIOLOGY Published by WFNMB Online: www.wjnm.org
  • 2. World Journal of Nuclear Medicine Volume 4, Supplement 1, October 2005 Editorial Padhy AK Therapeutic Nuclear Medicine: It is time to act S-1 WFNMB/WRPTC International Conference on Radiopharmaceutical Therapy Scientific Programme S-3 Abstracts S-12 Index of Authors S-66 World J Nucl Med 2005; 4: S1 - S67
  • 3. World Journal of Nuclear Medicine General Information Display Commercial Advertising This will be a publication of the World Federation of It is hoped that the nuclear medicine industry Nuclear Medicine & Biology (WFNMB) with the support (radiopharmaceuticals, nuclear instrumentation, computer of the IAEA and will be published quarterly. The & reagents etc.) will view the journal as an effective purposes of the journal are as follows: means of advertising to the nuclear medicine community. ! To be an official publication of the World Federation In order that the journal can be self-sustaining, we invite of Nuclear Medicine & Biology (WFNMB) with the the industry to provide significant support and to assist in active collaboration and support of the IAEA raising the profile of this important journal, the first to ! To promote research in nuclear medicine globally and specifically target the world-wide nuclear medicine in the developing countries in particular community. Besides regular full, half and quarter page ! To promote good practice in nuclear medicine advertisements, the journal will also publish special features like "windows for the industry". All advertising Target Group: materials accepted are expected to conform to ethical, ! All members of the WFNMB medical and business standards. Acceptance does not ! All member states of IAEA imply endorsement by the journal. ! Specialists belonging to various fields of nuclear medicine (Physicians, radiopharmacists, physicists, Editorial Office radioimmunoassayists, molecular biologists, etc.), World Journal of Nuclear Medicine technologists and nurses Nuclear Medicine Department ! Manufacturers of equipment and reagents relevant to KF Nuclear Diagnostics nuclear medicine Filiou Zannetou 10 ! Atomic Energy Commissions, Governmental and CY-3021 Lemesos administrative personnel relevant to nuclear medicine Tel.:+357 25878725 practice in the various countries Fax:+357 25871747 e-mail: A.K.Padhy@wjnm.org Contents: a.General: ISSN Number (print) 1450-1147 Reviews related to the good practice of nuclear medicine b. Related to WFNMB: Production Newsletter KF Nuclear Diagnostics Ltd. Announcements Filiou Zannetou 10 Reports of working groups, etc. CY-3021 Lemesos Editorials on WFNMB Planning & Strategy etc. Cyprus Abstracts of Congresses Tel.:+357 25878725 c. Related to IAEA and other International organizations: Fax:+357 25871747 Newsletter e-mail: info@nucleardiagnostics.com.cy Announcements Reports of CRPs, RCMs, Seminars Cover Design Abstracts of International Seminars Mr. Anatoli Bourykine (IAEA) Periodic world status reports Regional Windows Graphic Design Editorials Mr. Bankim Desai Cochrane Reviews d. Research & Development: Printers CMEs on Clinical subjects as well as on Science & Jagannath Printing Press, New Delhi, India Technology pertaining to nuclear medicine Original articles Electronic Edition Letters to the editor ISSN Number (online) 1607-3312 e. Windows for the Industry www.wjnm.org (coloured pages) WebMaster Marios Pieri, Nicosia, Cyprus Copyright © World Journal of Nuclear Medicine, 2005
  • 4. Editorial Board Editor in Chief : K.E. Britton Executive Editors : A.K. Padhy, H. Amaral, J.K. Chung Senior Editor : S. Frangos Editor (IAEA) : M. Dondi Treasurer : W. Choe Regional Editors : Africa: A. Ellmann, Asia: H. Sakahara, China & Fow East : M-Tian, Europe: A. Signore, N. America: C. Divgi, South and Central America: O. Estrella Anselmi, West Asia: M. Al-Zboun, Assistant Editors : A.Soricelli, G. Hinterleitner, N. Watanabe Members : M'Timet S (Tunisia) Aas M (Norway) Magzoub MAA (Sudan) Abdel-Dayem H (USA) Malamitsi J (Greece) Abdul Khader MA (Malaysia) Mather S (UK) Adel Bakir M (Syria) Maunda KKY (Tanzania) Al-Nahhas A (UK) McEwan AJW (Canada) Alvarado N (Peru) Meneghetti JC (Brazil) Andreo P (Sweden) Moustafa H (Egypt) Barrenechea E (Philippines) Mut F (Uruguay) Batista Cuellar JF (Cuba) Obaldo J (Philippines) Baum RP (Germany) Obradovic V (Serbia & Montenegro) Belohlavek O (Czech Republic) Olarrechea M (Bolivia) Bernal P (Colombia) Oliva JP (Cuba) Biersack H-J (Germany) Orellana P (Chile) Bouyoucef SE (Algeria) Palazzi F (Venezuela) Buscombe J (UK) Pant GS (India) Chaiwatanarat T (Thailand) Petrovici R (Romania) Chianelli M (Italy) Piepsz AM (Belgium) Corstens FHM (The Netherlands) Piperkova E (Bulgaria) Duffy G (Ireland) Prigent A (France) Dziuk M (Poland) Roca I (Spain) El-Desouki M (Saudi Arabia) Rodrigues Radischat M (Austria) El-Gazzar A-H (Kuwait) Rutland M (New Zeland) Fernandes O (Brazil) Saghari M (Iran) Fettich J (Slovenia) Salvatore M (Italy) Fonseca Zamora CA (Costa Rica) Samuel AM (India) Fraxedas R (Cuba) Sasaki Y (Japan) Garcia E (Mexico) Sixt R (Sweden) Goldsmith SJ (USA) Soroa V (Argentina) Gomo ZAR (Zimbawbe) Srivastava S (USA) Granowska (UK) Stabin M (USA) He Zuo-Xiang (china) Stare J (Slovenia) Henricksen JH (Denmark) Sundram FX (Singapore) Hesselwood S (UK) Szilvasi I (Hungary) Hoeflin F (Switzerland) Taiffeur R (Canada) Horne T (Israel) Thakur ML (USA) Hussein K (Indonesia) Tonami N (Japan) Hatton B (UK) Turner HJ (Australia) Jafri RA (Pakistan) Vassilakos PJ (Greece) Kabasakal L (Turkey) Vera Ruiz H (IAEA) Karim MA (Bangladesh) Viera R (Portugal) Knapp FF (USA) Vinjamuri S (UK) Kouris K (Cyprus) Virgolini I (Austria) Kropp J (Germany) Watawana L (Sri Lanka) Kumar V (Australia) Wenzel K von (Namibia) Lass P (Poland) Yonekura Y (Japan) Lepej J (Slovakia) Zakko S (UAE) Lind P (Austria) Zanzonico P (USA) Liu XJ (China) Zhang H (China)
  • 5. International Conference on Radiopharmaceutical Therapy (ICRT-2005) Limassol, Cyprus 11-14 October 2005 Venue: St Raphael Resort Limassol, Cyprus Organised by: World Radiopharmaceutical Therapy Council A subsidiary body of World Federation of Nuclear Medicine & Biology (WFNMB) In Collaboration with The Cyprus Society of Nuclear Medicine World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 6. December heralds the season of greetings and wishes. It is our great pleasure to invite you to the Annual conference of Society of Nuclear Medicine(India) of the year 2005 which is scheduled for coming December 08 to 11th in Calicut, Kerala. The theme of the conference "Scroll in to the era of Fusion Imaging" has been chosen to reflect the rapid changes and the future opportunities of Nuclear Medicine in India with a global perspective. Being one of the most beautiful places on earth, Kerala promises a wonderful experience to your expectation. For More Details Contact : Dr. G. Rijju Secretary General SNMI 2005 Department of Nuclear Medicine Malabar Institute of Medical Sciences (MIMS) Govindapuram PO Mini Bypass Road Calicut - 673 016 Kerala. INDIA. Tel : 0495-2744000 Fax : +91 495 2741329 Mobile : 9387521555 E-mail : snmi2005@gmail.com, drrijju@yahoo.com Website : http://www.malabarinstitute.com http://www.iasnm.org World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 7. S-1 Editorial Therapeutic Nuclear Medicine: It is time to act A.K. Padhy enhanced the scope and practice of radionuclide therapy Executive Editor, WJNM & Scientific Secretary-ICRT using radiopharmaceuticals prepared on site within the 2005 nuclear medicine-radiopharmacy dispensaries. The objectives of this conference are to evaluate the current It is my great pleasure inviting you to the First International status of radiopharmaceutical therapy in the world in Conference on Radiopharmaceutical Therapy (ICRT-2005) general and in the developing countries in particular, to being organised by the World Radiopharmaceutical exchange information on the current advances in the field Therapy Council (WRPTC). World Radiopharmaceutical between scientists from developed and developing Therapy Council is a subsidiary body of the World countries; to interact with user groups (clinicians, Federation of Nuclear Medicine and Biology (WFNM&B) oncologists, surgeons, radiopharmacists, medical with stake holders from all fields of nuclear medicine, physicists, etc.) and to bring them the most important several allied clinical specialties as well as from the information in the field, and to define future directions. industry including nuclear medicine physicians, radio- The Symposium will cover topics and issues on all aspects chemists, physicists, oncologists, rheumatologists, of radiopharmaceutical therapy through a number of endocrinologists and scientists, who share research plenary lectures, papers, panel discussions and interactive commitments to, and clinical practice in, therapeutic audiovisual sessions. The topics to be addressed at the nuclear medicine. The major objective of the WRPTC symposium include reviews in therapeutic radiopha- includes setting standards for provision of rmaceuticals, development of new radiopharmaceuticals, radiopharmaceutical therapy, particularly in the clinical overviews of the current trends in radionuclide development of uniform protocols for application therapy, clinical applications (radionuclide therapy of worldwide. primary cancers, treatment of metastatic disease, pain Radionuclides are being used extensively to provide palliation and treatment of benign diseases like rheumatoid palliative and curative treatment in a number of benign and arthritis, haemophilic haemarthrosis, hyperthyroidism malignant diseases. The potential of radionuclides for etc.), prognostication in cancer therapy, dosimetry, patient treating diseases has been recognized and put to use for the monitoring , molecular methods in radiopharmaceutical past several decades. It has been possible to exploit the therapy, treatment planning, use of new instruments physiology unique to an organ or a disease process to (PET/CT, dedicated cameras, hand held cameras, etc.) in deliver the radionuclides selectively to the sites of radiopharmaceutical therapy planning, drug resistance, abnormality. Radioiodine treatment of thyroid diseases radio-immuno detection and therapy, infrastructure (Thyroid cancer, Hyperthyroidism etc.), I-131 MIBG development , training and education. therapy of neuro-endocrine tumours, radio-immunotherapy Through organization of this conference we expect to of B-cell lymphoma, palliative treatment of metastatic bone accomplish the following: 1. To carry out an evaluation of pain using bone seeking radiopharmaceuticals, the current status of radiopharmaceutical therapy globally, radiosynovectomy and intravascular radionuclide therapy 2. To help in the transfer of important information on the using liquid sources of radioactivity to prevent restenosis in current trends in radiopharmaceutical therapy from patients following percutaneous Tran-luminal coronary developed to developing countries, 3. To publish a technical angioplasty (PTCA) have all been established in document based on the proceedings of the Symposium, 4. therapeutic nuclear medicine. The use of Rhenium 188 To promote radiopharmaceutical therapy globally in labelled compounds is rapidly increasing in the treatment of general, and in developing countries in particular and 5. To a number of benign and malignant disorders, including liver formulate a strategy document for promoting cancer (Re-188 Lipiodol), especially in developing radiopharmaceutical therapy around the world. countries. It is heartening to see overwhelming response to our efforts To-day radiopharmaceutical therapy is one of the fastest in the organization of this conference. We have a pre- growing branches of nuclear medicine. However, its conference registration of 175 participants and received practice in developing countries is only beginning to gain 122 abstracts for presentation. This is considered ground after years of trailing behind its use in the developed remarkable for a conference of this type. It is also world. The establishment and consolidation of remarkable that 70% of the abstracts received are from the radiopharmaceutical therapy has come about as a result of a developing countries, which in itself is an indication that gradual change in the realization of its importance, cost- radionuclide therapy is slowly but steadily being accepted effectiveness and practicality. Availability of new generator as a treatment modality in many parts of the developing produced, beta emitting radiopharmaceuticals like Re-188 world. for use in hospital radiopharmacy facilities has also It is expected that International organizations like World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 8. S-2 WFNMB, IAEA, WRPTC, SNM, EANM, ALASBMN, AOFNMB and ARCCNM as well as the radiopharmaceutical industry would rise to the occasion and take full advantage of this increasing awareness of therapeutic nuclear medicine. It is the time to act and provide the necessary impetus to this ever expanding branch of nuclear medicine. It is expected that meaningful discussions will be held in Cyprus during the conference and a solid road-map be created for the growth and development of radionuclide therapy in a global scale. This supplementary issue of the World Journal of Nuclear Medicine contains most of the abstracts of scientific papers and invited lectures to be presented at the ICRT-2005. The abstracts have been edited and formatted to the extent considered necessary for readers' assistance. The views expressed/ implied and the general style adopted remains however, the responsibility of the authors. I have really enjoyed immensely organizing this conference as its scientific secretary and I hope that we are going to have a wonderful time in Limassol celebrating ICRT-2005. Ajit Kumar Padhy World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 9. S-3 Programme Scientific Programme Monday: 10 October 2005 0900-1600 Registration, as participants start arriving in Cyprus 1900-2200 Pre-conference get-together Tuesday: 11 October 2005 0800-1600 Registration Time Abstract Title of Presentation Authors No. 0900-1030 Scientific Session-I: General Chairpersons: Hoefnagel C (The Netherlands), K. Kouris (Cyprus) USA-114 Future Directions in Bone-Localizing Srivastava S Therapeutic Radiopharmaceuticals USA-112 Therapeutic Applications of Rhenium- Knapp, Jr., F. F. 188 in Nuclear Medicine and Oncology - (Russ) Current Status and Expected Future Perspectives USA-117 Advances in targeted radioisotope Divgi C therapy in cancer. 1030-1100 Tea/ Coffee 1100-1300 Scientific Session-II: Thyroid-1 Chairpersons: San Luis TOL (Philippines), J. Kropp (Germany) UK-105 Radionuclide therapy of S. Vinjamuri Hyperthyroidism: An over view RSA-085 Treatment of Hyperthyroidism with Ellmann A Radioiodine: comparison of the efficacy of low, medium and high doses of I-131, with special emphasis on the socio- economic issues related to the treatment PHI-072 Therapeutic Options in the Management Barrenechea E et al. of Autonomously Functioning Thyroid Adenomas. CZR-021 Our experience with radioiodine therapy Kraft O of thyroid functional autonomies LAT-059 ¹³¹I therapy for euthyroid goitre in Berzina A et al. Latvia. MAL-063 Role of antithyroid drug treatment prior Das BK et al. to radioiodine therapy in hyperthyroidism IND-046 Incidence of micronuclei as biological Senthamizhchelvan dosimetry in differentiated thyroid S et al. carcinoma patients treated with 131I SLO-095 Recombinant Human TSH (rh TSH)- Schwarzbartl-Pevec aided radioiodine therapy in patients A et al. with differentiated thyroid carcinoma: Results 2002-4 World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 10. S-4 Programme Time Abstract Title of Presentation Authors No. Posters: Brief Reports BOH-123 Effect of radioiodine therapy on thyroid Rajkovca Z et al nodule size in patients with toxic adenomas BGD-010 Design & Development of a Lead Jar for Rahman Miah S et oral administration of radioiodine in al. hyperthyroid patients. IRA-052 Comparative Evaluation of the Two Esfahani AF et al. Fixed Dose Methods of Radioiodine Therapy (185 MBq and 370 MBq) for the Treatment of Graves' Disease. SER-087 Is drug-free period prior to radioiodine Han R et al. therapy decisive for treatment outcome in patients with multinodular toxic goitre? POL-078 A Retrospective Assessment of the Budlewski T et al. Effectiveness of Radioiodine Treatment of Hyperthyroid Patients from 1997 to 2003 in the North-Eastern Region of Poland. IND-048 Radioactive iodine (I-131) in treatment Sood A et al. of hyperthyroidism in Hilly Terrain Initial Experience. BGD-011 Radioiodine treatment for complicated Paul AK et al. hyperthyroidism using a fixed dose regime. CPR-020 Study of the therapeutic dose and the Dang Y et al. clinical effect on Graves' disease with 131I treatment LIT-060 Is it worth to calculate the dose of Mikalauskas V et al radioiodine? BGD-007 Experience and outcome of radioiodine Rahman Miah S et therapy in hyperthyroidism al. MON-064 Iodine-131 Therapy for the Treatment of Enkhtuya B et al. Hyperthyroidism 1300-1400 Lunch 1400-1600 Scientific Session-III Solid Tumour and Miscellaneous Therapy Chairpersons: B.A. Krishna (India), F.F. Knapp (USA) UK-103 Radiolabelled Aptamers for tumour A. Perkins imaging and therapy UK-100 Problems with antibody treatment of solid tumours Buscombe J GER-032 Intracoronary radiation therapy: Placebo Kropp J controlled study A Report. URU-111 Intravasular Radionuclide Therapy to Alonso O et al. prevent restenosis following PTCA JAP-057 Effect of Auger Electrons Internalized as Watanabe N et al. Indium-111 Labelled N-MYC Phosphorothionate Antisense Oligonucleotide (In-111-N-MYC-AS) on Human Neuroblastoma Cells: In vitro and In vivo studies World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 11. S-5 Programme Time Abstract Title of Presentation Authors No. Posters: Brief Reports IRA-056 Dose calculations of 186Re for Taghizadeh-asl M et production and feasibility of use to al. intravascular brachyherapy after coronary Angioplasty POR-082 Therapeutic Radiopharmaceuticals Neves M et al. UK-106 Radioimmunotherapy of Pancreatic S. Vinjamuri cancer with monoclonal antibodies BGD-006 Studies of therapeutic effects of Beta- Afroz S et al. radiation on Onchomycosis. IND-039 188 Re(V)DMSA -PLGA micro-spheres Shukla J et al. for targeted therapy of neurogenic tumors GRE-034 Labeling of a Bombesin analog with Koumarianou E et Rhenium-186 al. IND-050 A single vial method of preparation of I- Snehlata et al. 131 MIBG IND-051 Tele consultation and tele follow up of Pradhan PK et al. thyroid cancer patients A pilot study POL-079 Intravascular radionuclide therapy using Birkenfeld B et al. Re-188 Perrhenate to prevent re-stenosis following PTCA: Initial Experience in Poland SLO-096 Another case of metastatic malignant Žagar I et al. Struma Ovarii? A case report of good response to radioiodine therapy. UKR-108 Radionuclide therapy of true Afanasieva NI et al. polycythaemia SER-088 32-P Orthophosphorus in the Treatment Jaukovic L et al. of Polycythaemia Vera and Essential Thrombocythaemia BGD-013 Post-operative beta-irradiation in the Jehan AH et al. management of pterygium BGD-012 Use of strontium-90 beta irradiation as Nisa L et al. an adjunctive therapy for the management of squamous cell carcinoma of the conjunctiva POL-080 Sentinel Lymph node mapping and Birkenfeld B et al. detection in patients of melanoma: Role in prognosis PHI-076 Incremental value of nitrate Duldulao M et al. enhancement in Tc99m Sestamibi myocardial perfusion imaging with SPECT in patients with coronary artery disease and previous myocardial infarction AZB-005 Distant gammatherapy results of patients Shiraliyev OK et al. with esophagus cancer World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 12. S-6 Programme Time Abstract Title of Presentation Authors No. 1600-1730 Scientific Session-IV: Thyroid-2 Chairpersons: A. Perkins (UK), A. Staudenherz (Austria) CZR-023 International cooperation in the Kraft O et al. treatment of patients with differentiated thyroid cancers. IND-047 Optimizing the indications for Choudhury PS et al. radioiodine therapy as an adjuvant treatment in differentiated thyroid carcinoma. CPR-019 Retinoic acid in patients with Zheng R et al. radioiodine non-responsive differentiated thyroid carcinoma. ROM-083 Radioiodine therapy of differentiated Gherghe M et al. thyroid cancer in patients with negative diagnostic I 131 scintigraphy and high serum thyroglobulin level IND-043 Treatment of differentiated thyroid Krishna BA et al cancer using Recombinant TSH injection AUS-004 Statins As A New Therapeutic Approach Hofmann A et al. In Dedifferentiated Thyroid Cancer? A Case Report PHI-075 Prospective Randomized Trial for the Barrenechea EA et Evaluation of the Efficacy of Low Vs. al. High Dose I-131 for Post Operative Remnant Ablation in Differentiated Thyroid Cancer BUL-016 99mTc-MIBI and 131I scintigraphy in the Sergieva S et al. follow-up of differentiated thyroid carcinoma (DTC) patients after surgery. Posters: Brief Reports PHI-073 The Value of PET in DTC with Barrenechea EA et Negative WBS but Elevated al. Thyroglobulin levels IRA-055 Study of ablation efficiency of 3600 Takavar A et al. MBq of I-131 in the Treatment of Thyroid Carcinoma UKR-107 Sialoscintigraphy with 99m Tc- Korol P pertechnetate in evaluation of salivary gland function in patients with differentiated thyroid cancer after radioiodine therapy IRA-053 The Rate of Depression and its Risk Eftekhari M et al. Stratification in Patients With Differentiated Thyroid Cancers Treated With Radioactive Iodine BGD-008 Success of Repeated I-131 Therapy in Alam F et al cases of Metastatic Differentiated Thyroid Carcinoma World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 13. S-7 Programme Time Abstract Title of Presentation Authors No. IND-040 Our experience with the treatment of Anand YNI et al. 155 cases of carcinoma of the thyroid IND-049 Evaluation of medullary carcinoma Krishnakumar R thyroid. IND-044 Our Experience of High Dose I-131 Dougall P et al. Therapy in 75 patients with Well Differentiated Carcinoma Thyroid Followed Up Over 5 years UKR-109 Up to date programme of treatment and Afanasieva NI et al. long-term follow-up of the patients with differentiated thyroid carcinoma PER-071 Influence of T-3 produced by metastatic Mendoza G et al. thyroid tissue on I-131 treatment outcome. BGD-014 Second malignancies following the Yashmin S et al. treatment of differentiated thyroid carcinoma with radioiodine SRL-097 Radioiodine (I131) application in the Nanayakkara D management of differentiated thyroid cancer (DTC) Audit IND-045 Air Monitoring in Radioiodine Therapy Sarika et al. Ward 1900 Opening Ceremony Followed by: Gala Dinner Wednesday: 12 October 2005 0800-1200 Pre-lunch Guided educational tour of Cyprus 1200-1400 Lunch at a Fish Taverna Scientific Session-V Luncheon Meeting : Special Session on WRPTC Chairpersons : Turner H (Australia), S. Srivastava (USA) Brainstorming : WRPTC: How to proceed from here, New Ideas, Future Directions (All Participants) 1400-1800 Post-lunch Guided educational tour of Cyprus Thursday: 13 October 2005 0830-1030 Scientific Session-VI: Bone Pain Palliation & Miscellaneous Chairpersons: A. Ellmann (S. Africa), E. Barrenechea (Philippines) USA-118 The role of imaging in planning therapy C. Divgi in cancer. World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 14. S-8 Programme Time Abstract Title of Presentation Authors No. UK-104 C-595 Antibody: A potential vector for A. Perkins targeted alpha therapy GER-028 Radionuclide therapy in palliative Liepe K treatment of metastatic bone disease: Review IND-038 Sm-153 EDTMP therapy for bone pain Tripathy M et al palliation in skeletal metastases: AIIMS Experience. PAK-068 Formulation and evaluation of Beta- Muhammad S et al emitting radionuclide labelled EDTMP for bone pain palliation. ROM-084 Use of Sr-89 for bone pain palliation: Mititelu R et al. Experience in our department. PER-070 Impact of educational strategies in Seminario C et al. positioning Samarium-153 EDTMP as a treatment for pain due to bone metastases. LIT-062 Bone pain palliation with strontium-89 Tiskevicius S et al in cancer patients with bone metastases GRE-036 Comparative Study of Skeletal Papanikolos G et al. Dosimetry Methods in Therapeutic Schemes with Re186 HEDP and Sm 153 EDTMP Posters: Brief Reports POL-081 188W/188Re generator as a convenient Mikolajczak R et al. source of 188Re perrhenate solution and a kit for preparation of 188Re-HDEHP IRA-054 Strontium-89 in Palliative Treatment of Haddad P et al. Widespread Painful Bone Metastases: Response Rate and Duration UKR-110 Combination Radiation Therapy for Afanasieva NI et al. Bone Metastases in Thyroid Cancer SLO-093 Radionuclide Therapy in Slovenia Fettich J DOM-024 Radiopharmaceutical Therapy in de los Santos JO Dominican Republic. Present and Future UZB-121 Nuclear Medicine in Uzbekistan & Rasulova N et al. Current status of Radionuclide therapy in the country EGY-025 Osteosarcoma target therapy with stem Fawzy A cell transplant A case review 1030-1100 Tea/ coffee 1100-1300 Scientific Session-VII: Radiosynovectomy Chairpersons: AH Elgazzar (Kuwait), P. Bernal (Colombia) GER-030 Radiosynovectomy; A Review Liepe K VEN-122 Radiosynoviorthesis Fernando Palazzi F BRA-015 Use of Samarium 153 Hydroxyapatite Anselmi OE et al. for intra-articular therapy World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 15. S-9 Programme Time Abstract Title of Presentation Authors No. PHI-074 Comparative evaluation of the efficacy Barrenechea EA et of radiosynovectomy with conventional al. intra-articular therapy in rheumatoid arthritis and haemophilic arthropathy (CERAHA) ALG-001 Use of radiosynoviorthesis with Y-90 in Bouyoucef SE et al. the treatment of Persistent knee hydarthrosis SLO-094 The Efficacy of Radiosynoviectomy in Grmek M et al. Hemophilic Hemarthrosis According to the Frequency of Joint Bleedings IND-037 Radiation synovectomy versus intra- Solav S articular steroid treatment in inflammatory arthritis Posters: Brief Reports MON-066 Radiation synovectomy with 188Re-tin Erdenechimeg S et colloid in histological study al. ARG-002 Two-year results of radiosynovectomy Soroa V et al in knee-joints of Hemophilic patients using locally developed P-32 colloid. SLK-092 Evaluation of the Efficacy of Vereb M et al. Radiosynovectomy in Rheumatoid Arthritis and Haemophilic Arthropathy (CERAHA): First Results of an IAEA Co-ordinated Research Project (CRP) EST-026 Radiosynovectomy: first results in Nazarenko S et al. Estonia CZR-022 Our experience with radiosynoviorthesis Kraft O et al. and re-radiosynoviorthesis of knees. IND-041 Comparison of musculoskeletal USG Ray S et al. and radionuclide soft tissue scintigraphy in the evaluation, selection and follow- up of patients for radiosynoviorthesis 1300-1400 Lunch 1400-1600 Scientific Session-VIII: Lymphoma/ Other Haematological Malignancies and Liver Cancer Chairpersons: H. Amaral (Chile), J. Buscombe (UK) USA-120 Role of Radionuclides in Therapy of Wiseman G Haematologic Malignancies. SIN-091 Radioimmunotherapy of Refractory B- Sundram FX Cell Lymphoma GER-033 Radionuclide Therapy of B-NHL with Kropp J 90-Y-Epratuzumab: A report of the multi-centre trial AST-003 I-131 Rituximab (chimeric anti CD 20 Turner JH Mab) radioimmunotherapy of non- Hodgkins lymphoma World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 16. S-10 Programme Time Abstract Title of Presentation Authors No. IND-042 Impact of FDG-PET imaging in the Krishna BA treatment of Lymphomas: Indian experience UK-101 Radionuclide treatment of Liver Cancer Buscombe JH using I-131 Lipiodol A review UK-102 Use of Y-90 lanreotide and Y-90 Al-Nahhas A microsheres in treatment of liver tumours. SIN-090 Experimental therapy with P-32 for Goh A et al. hepatoma COL-018 Radionuclide treatment of Liver Cancer Bernal P et al. using Re-188 Lipiodol Posters: Brief Reports PAK-069 Trans-Arterial Radioconjugate Asghar S et al. Radionuclide Therapy For Hepatocellular Carcinoma; Feasibility & Applications In Pakistan PHI-077 Radionuclide treatment of Liver Cancer San Luis TOL et al. using Re-188 Lipiodol: Experience in Philippines SER-086 Possible Role of the Scintigraphic Artiko V et al. Estimation of the Relative Liver Perfusion in the Choice of Treatment of Liver Carcinomas. SIN-089 [Re(CO)3]-Chelates as Therappeutic Saw MM et al. Radiopharmaceuticals for the treatment of Hepatocellular Carcinoma MON-065 Treatment of HCC with Re-188 lipiodol Erdenechimeg S Initial experience in Mongolia THA-098 First Experiences in 90Y-Zevalin For Saesow N et al. Treatment of Non-Hodgkin's Lymphoma in Thailand. 1600-1730 Scientific Session-IX: Neuro-endocrine Tumours Chairpersons : M.C. Lee (Korea), V. Soroa (Argentina) UK-099 Pathophysiology and non-radionuclide therapy of neuroendocrine tumours Buscombe J GER-029 Peptide Receptor Radionuclide Therapy Baum R (PRRT) of Neuroendocrine Tumors Using Y-90 and Lu-177 Labeled Somatostatin Analogs: Principles, Technique and Clinical Results after 500 Treatments NET-067 Interventions in 131I-MIBG treatment of Hoefnagel CA neuroendocrine tumours GRE-035 Patient specific dosimetry of I-123 Lyra M et al. MIBG in diagnosis for improvement of dose estimation in I-131-MIBG adrenal tumours therapy World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 17. S-11 Programme Time Abstract Title of Presentation Authors No. GER-031 Peptide Receptor Radionuclide Therapy Wehrmann C et al. (PRRT) of Neuroendocrine Tumors: First Comparative Results using the Somatostatin Analogues Lu-177 DOTA- NOC and Lu-177 DOTA-TATE Posters: Brief reports CHI-017 Peptide receptor radionuclide therapy Amaral H with Y-90 DOTATOC (Somatostatin analogue) in neuroendocrine tumours: The Chilean Experience LIT-061 Somatostatin receptor imaging and Kulakiene I et al. therapy an ever expanding choice EST-027 Our first experience in the application of Samarina G et al. 131I-MIBG in a patient with neuroblastoma (case report). BGD-009 Targeted therapy of neuroblastoma with Hussain R et al. I131 -MIBG: experience of 15 cases. 1930 Dinner & Cyprus Night Friday; 14 October 2005 0830-1030 Scientific Session-X : Development of new radiopharmaceuticals, Intracellular targeted therapy and Molecular Imaging in Radionuclide Therapy Chairpersons: Baum R (Germany), Nazarenko S (Estonia) USA-113 Therapy with High LET Radioisotopes Knapp, Jr., F. F. Can Sufficient Levels of Attractive (Russ) Auger and Alpha Emitters be Produced to Make Their Use Practical? USA-116 Development and Evaluation of High Cutler CS et al Specific Activity Radioisotopes for Radiotherapy KOR-058 Role of PET for monitoring the Lee MC therapeutic response USA-119 Incorporating FDG PET Imaging in the Wiseman G Response Criteria for Non-Hodgkin's Lymphoma USA-115 Radiolabeled Adenoviral Sub-Unit Srivastava S Proteins for Molecular Imaging and Therapeutic Applications in Oncology 1030-1130 Closing World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 18. S-12 Abstracts: ICRT-2005 001-ALG hemophilic patients, ages ranging from 4-52 years. Nine patients Use of Radiosynoviorthesis with Y-90 in the Treatment of had re-treatments either in the same or in the contralateral knee, Persistent Knee Hydarthrosis making it a total of 67 procedures in the study. In adults, a dose of Bouyoucef SE1, Henni-Haddam F2, Sellah M3, Aouli S3, 37-74 mCi was used, while 33% of this dose was used in children Benlabgaa R 1 ,Hanzal A 1 , Mansouri B 3 , Abtroun S 2 ; between 2-6 years, 50% in children between 6-10 years and 75% 1 Department of Nuclear Medicine, CHU Bab El Oued, Algiers; in children between 10-16 years of age. Patients with Grades II & 2 Department of Rhumatology, CHU Bab El Oued, Algiers; III arthropathies were included in the study. Informed consents 3 Department of Radiology, CHU Bab El Oued, Algiers, Algeria from adults and from the parents of children were obtained. Patients with large Bakers cyst, grade IV arthropathy, infection in The objective of this study is to determine the treatment success the skin around the joint area and bleeding at the time of the rates and factors predicting successful outcome when using procedure were excluded from the study. Documentation clinical yttrium-90 intra articular injections as treatment of persistent knee history and AHF therapy was done in all cases. All patients hydarthrosis refractory to other treatments. 68 patients, 41 with underwent three phase bone scans before therapy and after therapy rheumatoid arthritis, 9 with ankylosing spondylarthritis, 6 with at 1, 3 6, 9 and 12 months. If required, joint aspiration was carried Behcet disease, 6 with psoriatic arthritis, and 6 patients with out. P-32 Bremsstrahlung emission was used in the scintigraphies gonarthritis, with a total of 121 knees have been treated by Yttrium for early and late imaging to confirm the presence or absence of 90 (Y90) for a persistent hydarthrosis. Mean duration of the knee leakage. All patients were subjected to immobilization of the effusion was 4.85 years(range 1 to 20 years) and mean number of treated joints and relative rest for a period of 72 hours following intra articular steroid injection was 3.85 (range 1 to 20 steroid therapy. injections). According radiological classification of Steinbrocker, There were no local or systemic adverse effects following 68 knees were in stage I and 53 were in stage 2. Pain, mobility, treatment. No leakage of radioactivity was detected in any of our volume effusion and needs to further intra articular steroid patients. Intraarticular Rifampicin procedure required frequent injection were the main parameters to evaluate the outcomes of the injections. The follow-up evaluation demonstrated significant radiosynovectomy. Outcomes were assessed for each patients as improvement of joint motion, diminished knee volume and less 'excellent improvement', 'good improvement', 'fair improvement' requirement and frequency of the use of Anti-haemophilic Factors or 'not improved' by review of the case notes at 3, 6,12,18,24 (AHF) in 80% of patients subjected to radiosynovectomy (54 /67 months. Excellent and good outcomes were equal to 63.2% at 3 procedures), thus lowering treatment costs. Remission Indices months, 66% at 6 months, 65.9 % at 12 months, 59% at 18 months (rate of change of lesion activity over time) calculated over the and 53% at 24 months. By aetiology, best score, for excellent and treated joints using sequential Tc-99m MDP soft tissue good outcomes, was observed for Behcet disease(100% at 12 and scintigraphy revealed significant reduction of lesion activity 24 months) and for rheumatoid arthritis (83% at 6 months). Best objectively. outcomes were also obtained when knees are classified at Overall it has been observed that one intra-articular knee radiological stage 1 ( 66% at 6 and 12 months) and when knee radiosynovectomy procedure using P-32 colloid in patients with effusion duration is inferior to 2 years ( 78% at 12 months). No haemophilic arthropathy could provide relief from symptoms for a significant improvement was observed for knees at stage 2 and period of 3-6 months. We have found radiosynovectomy to be ankylosing spondylo-arthritis (49% with no improvement at 6 safe and cost-effective and recommend its use as an alternate months). Radiosynoviorthesis treats successfully patients with therapeutic procedure where availability of AHF is difficult and persistent knee effusion refractory to other therapies. Patients with expensive. Behcet disease and rheumatoid arthritis, less destructive radiographic changes, shorter duration of joint disease, tend to 003-AST respond more favourably and have good outcomes. I-131 Rituximab (Chimeric Anti Cd 20 Mab) Radioimmunotherapy of Non-Hodgkins Lymphoma 002-ARG: Turner JH, The University of Western Australia, Fremantle Two-year Results of Radiosynovectomy in Knee-joints of Hospital, Alma Street, Fremantle WA 6160 Australia Hemophilic Patients Using Locally Developed P-32 Colloid. Soroa V, Velázquez Espeche MH, Giannone C, Caviglia H, Galatros Commercially available anti-CD 20 monoclonal antibody, G, Nicolini JO Centro de Medicina Nuclear, Comisión Nacional de rituximab (MabThera®) may be efficiently radioiodinated with Energía Atómica Argentina, Buenos Aires, Argentina; Traumatology 131I using standard Chloramine-T methodology in a hospital & Orthopedics, Htal. Municipal J. A. Fernández, Hemophilic radiopharmacy, under appropriate regulatory authority approvals. Foundation, Buenos Aires, Argentina; Radiopharmacy, Lab. Bacon, Multicentre clinical trials of 131I-rituximab radioimmunotherapy Buenos Aires, Argentina. have been performed in patients with relapsed or refractory low grade non-Hodgkins lymphoma with therapeutically effective The aim of this study was to assess the effects of radionuclide administered activities being determined on the basis of treatment of haemophilic arthropathy of knee joints refractory to individualised prospective patient dosimetry. A non- conventional medical therapy with the locally developed P-32 myeloablative regimen of 131I-radioimmunotherapy predicated colloidal suspension in Argentina, and compare the results with those upon a maximum prescribed dose of 0.75 Gy to whole body has of chemical synovectomy, and to assess the cost/ effective aspects of been used to minimise myelotoxicity in patients undergoing radiosynovectomy. It may be noted that other imported colloidal radioimmuno-therapy, even when they have been heavily radiopharmaceuticals like Y-90 citrate, Re-186 sulfide or Er-160 pretreated with chemotherapy and/or there is tumour infiltration citrate are expensive in Argentina. On the other hand we have the of bone marrow greater than 25%. Provided that baseline technology to prepare Ho-166 macro-aggregates in Argentina, but the radiopharmaceutical has not been approved for use on humans by the leucocytes exceeded an absolute neutrophil count of 1.5 x 109/L country's regulatory authorities. and platelets > 100 x 109 /L, the incidence of grade IV Radiosynovectomy was performed using P-32 colloid in 58 male haematological toxicity was 16% for neutrophils and 4 % for World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 19. S-13 Abstracts: ICRT-2005 platelets which was self-limited. The red marrow radiation 004-AUS absorbed dose in selected patients receiving 131I activities Statins As A New Therapeutic Approach in Dedifferentiated estimated to deliver 0.75 Gy to whole body was calculated to be Thyroid Cancer? less than 2 Gy using Monte Carlo methodology on post therapy A Case Report CT/SPECT imaging. A. Hofmann, P. John, M.P. Schaffarich*, H. Sinzinger, A. Predictive dosimetry was performed by serial whole body Staudenherz imaging following IV administration of a standard 200 MBq 131I- Univ. Clinic of Nuclear Medicine, Medical University of Vienna, rituximab tracer and determination of individual Austria & *Centre for Biomedical Engineering and Physics, pharmacokinetics of the radiolabelled antibody in each patient. A Medical University of Vienna standard dose of 375 mg/m2 unlabelled rituximab (MabThera®) was administered IV immediately prior to the tracer and therapy In general differentiated thyroid tumours are removed surgically doses of 131I-rituximab to minimise nonspecific uptake of the and afterwards treated with radioiodine. However, still about one radiolabelled antibody and to optimise the tumour to background third of patients with differentiated tumours, metastasise. Also 30 activity. The administration of a standard course of 4 cycles of percent of recurrent thyroid carcinomas do not respond to iodine cold rituximab (MabThera®) in association with the prescribed treatment due to loss of differentiation. Retinoic acid, biological maximum activity of 131I-rituximab constitutes metabolites of vitamin A, are considered to induce re- radioimmunotherapy rather than antibody-targeted internal differentiation of the thyrocyte and thereby induce tumor radiotherapy. Such treatment in 90 patients with regression. In follicular carcinoma cells, it also plays an important relapsed/refractory follicular (grade I, II, III) (78) MALT (5) and role in inducing iodine uptake. Retinoids, however, cannot be used small lymphocytic (7) lymphoma with 3 (1-8) median prior in liver disease as they may induce hepatic enzyme increase. In chemo-therapies, 60% stage III/IV, resulted in complete remission addition 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) (CR) in 51% and partial response (PR) in 23% for an overall reductase inhibitors (statins) are reported to induce on the one response rate (ORR) of 74%. In contrast to radiolabelled murine hand cellular apoptosis and on the other hand, in a lower dosage, antibodies, the 131I-rituximab chimeric monoclonal antibody differentiation in anaplastic thyroid carcinoma cells in vitro. does not cause any immunogenic HAMA host response and We are presenting a 79 years old female patient with an oxyphilic repeated courses of 131I-rituximab radioimmunotherapy may be follicular thyroid carcinoma and histologically verified given for subsequent relapse. The median duration of response autoimmune hepatitis. The first posttherapeutic scan, showed only was 22 months in our patients who achieved CR and retreatment focal cervical localized ioidine uptake. Also 3 months later no was performed in 8 patients, the majority of whom responded pathologic iodine uptake was recognized on the diagnostic scan, again to the repeat 131I-rituximab radioimmunotherapy. Median whereas the FDG-PET showed solid uptake of FDG cervical, in progression-free survival in our patients was 13 months and the 4 both lungs, in the mediastinum, the pelvis and the right hip. Due to year actuarial survival of all our treated patients after 131I- contraindication for retinoic acid the patient was treated with rituximab radioimmunotherapy for non-Hodgkins lymphoma was usual dose statin for about 4 weeks to induce re-differentiation. 63%. Following, the patient was administered 9,25 GBq I-131 again and Non-myeloablative radioimmunotherapy of mantle cell non- the posttherapeutic scan showed iodine uptake cervical and in the Hodgkins lymphoma with 131I-rituximab showed CR in 2 of 8 right femur. patients, but the reported results of myeloablative regimens and We conclude that the administration of Statins, at low dose (20 autologous stem cell rescue demonstrate CR in 6 or 7patients after mg/day) even over a short period of time, only may induce re- 131I-rituximab treatment. Indolent non-Hodgkins lymphoma differentiation as well as an antiproliferative effect in vivo which transforms into more aggressive forms may also be treated with a myeloablative regimen combining standard dose 131I- 005-AZB rituximab radioimmunotherapy with BEAM chemotherapy for Distant Gammatherapy Results of Patients With Esophagus conditioning prior to stem cell autograft at 16 days. Three patients Cancer. with transformed non-Hodgkins lymphoma treated with 131I- Shiraliyev O.K., Beibutov Sh.M., Quilieva A.O., Nasirova F.J. rituximab, BEAM chemotherapy and stem cell rescue all achieved Dept. of Nuclear Medicine, Republic Diagnostic center & CR of duration of at least 12 months. Refractory or relapsed Azerbaijan, Dept. of Nuclear Medicine, National Cancer Centre, aggressive non-Hodgkins lymphoma such as DLCBL may also be Azerbaijan treated with nonmyeloablative protocols complemented by long- term consolidation and maintenance MabThera immunotherapy, The problem of esophagus cancer therapy gains the particular currently in clinical trial. Greater experience has been obtained meaning for Azerbaijan where this disease incidence exceeds the with 131I tositumomab (Bexxar® ) in both marrow sparing parameters of neighboring countries by almost two times. 1240 radioimmunotherapy of relapsed and first line treatment of low patients with esophagus cancer were under our observation for grade non-Hodgkins lymphoma and in myeloablative protocols of more than 15 years who had been subjected to the distant static radioimmunotherapy of aggressive or refractory non-Hodgkins gamma therapy on apparatuses “Agat-R” and “Rockus M”. there lymphoma with bone marrow transplantation. This clinical were 732 men (59 % )and 508 women (41 %) . The patients' age experience with radioiodinated murine anti CD 20 Mab ranged from 24-88 years. Disease duration since the appearance of radioimmunotherapy will be compared with that of 131I- the first symptoms till entering to the department was 4-8 months rituximab chimeric antibody radioimmunotherapy of non- on the average. Hodgkins lymphoma. Esophagus cancer is often localized in the places of the physiological stenosis. So tumour was lacalised in the neck region esophagus in 45 patients (4.1%), in upper pectoral in 104 ones ( 9.5%), in middle pectoral in 594 ones (54.5%) in lower pectoral in 299 ones (27.4%) in abdominal regions of esophagus 48 World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 20. S-14 Abstracts: ICRT-2005 patients(4.5%).The extent of dimensions of tumour esophagus randomised in three groups. Group A (n =110) received was ranged within 2-13 cm, only it was less than 5 cm in 6.5% griseofulvin orally 500mg once daily for 12-16 weeks; Group B patients. (n=110) received beta radiation, 500 rads bi-weekly for 3 weeks The opportune surgical treatment ensures the perfect recovery. (total 2500 rads); and Group C (n=110) received combined beta However, the early stage of the disease can develop radiation (total 2500 rads in 3 weeks) and griseofulvin (500 mg asymptomatically. The patients with the 1st stage of lesion were daily for 6 weeks). Patients were followed up for 24 weeks. only 8 (0.8%) with the 2nd one 408(37.4%), with the 3rd one Efficacy of the treatment was evaluated in all 287 patients while 607(55.7%), with the 4th one 67(6.1%). Radiation therapy was 43 (13.03%) cases were dropped out from the initial allocation. applied in the cases of inoperable and also in patient who were At the end of the follow up period (6 months after discontinuation older than 60 or refused operation. 1090patients (88%) finished of treatment) mycological cure rate was achieved 41 (42.70%), 36 the treatment course. Local summary doses have formed 50-70 (38.70%) and 65 (66.33%) in Group-A, Group-B and Group-C Grey , the momentary ones-2-2.5 Grey on the medium. The rest of respectively. The mycological cure rate was highly significant the patients haven't finished the treatment due to several reasons. (P=0.000) and considered to be the acceptable outcome of The results of the treatment are as follows: We observed clinical treatment. Clinical cure rate was considered as another way of cure in 389 patients (35.7%) , an improvement in 541 (499%), the assessment. Percentage of clinical cure rate was similar as process stabiliation or an absence of effect in 160 (14.3%). 40.1% mycological cure rate and equally significant (P=0.000). of patients lived for more than 1 year, 18.4% for more than 2 Recurrence rate of the disease was highest in griseofulvin-induced years,12.0% for more than 3 years and 7.0% for more than 5years. patients 21 (21.88%) and in beta radiation exposed patients was 14 It was established that the best results were obtained in case of (15.06%). This rate was least in combination therapy group of tumour location in the middle and lower regions of esophagus. griseofulvin and beta radiation 4 (4.08%). Cure rate in Group C is We concluded that radiation has a palliate effect with the significantly higher than Group A and B as well (P=0.000). temporary stabiliztion, partial or nearly complete regression of Several known side effects causing systemic involvement of oral tumour in most patients and saves a lot of patients suffering from drugs are already being experienced, side effects like blackening the severe symptoms. Radiation treatment of esophagus cancer is of surrounding soft tissue of nail were observed which were recommended as a routine in oncological establishments. transient and self-limiting. Further to this, all sample population underwent for biochemical and haematological tests pre and post 006-BGD radiation application. No significant change of tests results were Therapeutic Effect of Beta Radiation on Onychomycosis an observed excluding any observable radiation side affects to this Innovative Treatment particular type of radiation application. Afroz S, Islam N, Rashid H, Shahidullah M, Ali S, Islam S K M, It can be concluded that the proposed new beta radiation treatment Hossain S, Ali N modality for onychomycosis exhibited a low risk- benefit ratio. It Centre for Nuclear Medicine & Ultrasound, Dhaka Medical is well-tolerated and efficacious method to treat onychomycosis. College Hospital, Dhaka-1000, Bangladesh From the observations of the present study it may be considered worthy to comment that in Group C as the cure rate is highest, Onychomycosis is the most frequent cause of nail disease and the recurrent rate is the lowest, duration and cost of treatment are most prevalent type of dermatophytosis in Bangladesh. The humid significantly less, this modality of treatment can be considered as and warm climate of this tropical country is congenial for the the more acceptable procedure for management of growth of fungi. Therapeutic limitations of conventional onychomycosis in a developing country like Bangladesh. Group antimycotic agents in respect of low cure rates, high relapse rate, B (beta radiation only) can also be accepted in special occasions to inherent side effects, long duration of treatment and high cost in replace Group A (Antifungal). treating onychomycosis have provided clear incentives to explore This innovative treatment procedure could be introduced in other alternative forms of treatment procedure. Nuclear Medicine Centres of the country with a view to expand the The objectives of the present thesis work were: procedure, so that large number of patients could be beneficiary as (i) To use beta radiation as a curative therapy for end users. Onychomycosis, optimisation of its dosages and to promote Afroz S1. Director, Centre for Nuclear Medicine & Ultrasound, an innovative clinical development in the field of therapeutic Dhaka Medical College and Hospital (DMCH); Islam N2. application of nuclear medicine Professor and Chairman, Department of virology, BSSMU, (ii) To assess the efficacy of beta radiation either alone or in Dhaka; Rashid H3. Principal Physicist, Centre for Nuclear combination with conventional antifungal therapy; and Medicine & Ultrasound-DMCH; Shahidullah M4, Professor and (iii) To reduce the duration of drug exposure and cost of treatment Head, Department of Dermatology and veneriology-DMCH, Ali for onychomycosis. S5. Professor of Biochemistry, BSMMU & Member Public This is a PhD research work under the University of Dhaka and Service Commission, Islam S K M6. Associate Professor, Dept. of was sponsored by the Ministry of Science and Information & Microbiology, SSMCH, Hossain S7 . Associate Professor, Centre Communication Technology, Government of the people's republic for Nuclear Medicine & Ultrasound-DMCH; Ali N8. Biochemist, of Bangladesh. This study is an open, randomised and controlled Department of Bio chemistry-DMCH. trial to verify the efficacy of beta radiation in patients with onychomycosis. Using the appropriate statistical formula, sample size of the study population was determined and in each group 92 patients were assigned. With an assumption of patients drop out and for better statistical analysis, a total of 330 patients, who fulfilled the inclusion criterion having diagnosed to have onychomycosis clinically and mycological were randomly allocated to enter in therapeutic regimen. Study population was World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 21. S-15 Abstracts: ICRT-2005 007-BGD as per advice and 13 patients were lost to follow up. It was found Experience and outcome of Radioiodine Therapy in that 18 patients became euthyroid within 3 months, 35 patients Hyperthyroidism became euthyroid within 6 months, 19 patients became euthyroid Miah SH, Paul AK, Rahman HA within 9 months and 97 patients became euthyroid within 1 year. Centre for Nuclear Medicine & Ultrasound, Khulna, Bangladesh Thus the cure rate was found to be 88.95% (169/190). In 18 (9.47%) cases hyperthyroidism persisted with no clinical and Radioiodine is being increasingly used in the treatment of biochemical improvement within 6 months in which 15 were hyperthyroidism. The primary reasons for choosing radioiodine Graves' disease, 1 solitary toxic nodule and 2 toxic multinodular therapy are its effectiveness, ease of administration, relatively low goiter. After becoming euthyroidism, hyperthyroidism recurs in 3 cost and paucity of side effects. Here we presented our experiences (1.58 %) cases within 1 year. Recurrence of hyperthyroidism was and outcome of radioiodine therapy in hyperthyroidism in a also seen in 2 cases after 1 year of radioiodine treatment. These divisional referral centre.We retrospectively analyzed 203 patients (persistent and recur cases) were treated with second dose patients receiving radioiodine therapy for hyperthyroidism in and if needed third and/or fourth dose of radioiodine. Second dose Centre for Nuclear Medicine & Ultrasound, Khulna during the was given in 23 cases, third dose given in 7 cases and fourth dose period from July 1994 to June 2004. All the patients had clinical given in 2 cases. We referred 1 case for surgical treatment not for signs and symptoms of hyperthyroidism as well as elevated responding even with fourth dose of radioiodine. During our triiodothyronine (T3), thyroxine (T4) and suppressed thyroid follow up period, 6 patients became hypothyroid within 3 months, stimulating hormone (TSH). T3, T4 and TSH were done in all cases. 14 patients became hypothyroid within 6 months, 7 patients Radionuclide scan and ultrasound of thyroid gland, radioactive became hypothyroid within 9 months and 5 patients became iodine uptake (RAIU), thyroid microsomal antibody (TMAb) and hypothyroid within 1 year. Thus hypothyroidism within 1 year fine needle aspiration cytology (FNAC) was done in selected was found to be 16.84% (32/190). Other side effects such as cases. We assessed all patients prior to radioiodine therapy. iododerma were observed in 5 (2.63%) cases, radiation thyroiditis Elderly patients and all those with cardiac complications and developed in 17 (8.95%) cases, thyroid storm developed in 2 severe hyperthyroidism were pretreated with a short course of (1.05%) cases. Out of 43 with ophthalmopathy, 2 (4.44%) antithyroid drug in full dosages until they were clinically and deteriorated, 1 (2.32%) unchanged and the rest (93.02%) biochemically euthyroid. Ninety five patients were on antithyroid improved. New ophthalmopathy developed in 3 cases (3/147 i.e., medication (Neomercazole) prior to radioiodine therapy. 2.04%). None developed any malignancy or leukemia during our Antithyroid medication were stopped 3 days before radioiodine follow up period. We conclude that our experience revealed therapy and restarted 3 days later and continued for 1 to 2 months similar outcomes as have been reported by other workers with the depending on patient's symptoms. The rest of the patients exception of iododerma, one of the early complications of received either no treatment or beta-blocker prior to radioiodine radioiodine therapy that we noticed during our follow up period. therapy. Menstrual history was taken in female patients and pregnancy was excluded by ultrasonography in doubtful cases 008-BGD before administering radioiodine. The likely consequences of the Success of Repeated I-131 Therapy in Cases of Metastatic treatment were fully explained to the patients and attendants, the Differentiated Thyroid Carcinoma usual precautions for radiation protection of the public and the Alam F, Kabir MF, Karim MA. Institute of Nuclear Medicine, necessity of the follow-up were discussed and verbal consent was BAEC, BSMMU, Dhaka taken before administering radioiodine. Radioiodine was given orally as Na131I solution to all patients in modified fixed dose Differentiated Thyroid Carcinoma (DTC) is not an aggressive regime ranged from 5 mCi to 15 mCi. All the patients were advised malignancy and its treatment is very promising. The treatment is to attend the centre if any complications arise and in regular follow performed by surgery only (in selective cases) or by surgery up at 6 weeks, 3 months, 6 months, 9 months and 1 year and then followed by I-131 therapy. Treatment of metastasis is equally annually. Clinical and biochemical evaluations were done in effective but difficult in cases of lung and bone metastases. The follow up visit. If the first dose was found to be ineffective in objective of this study was to see the effectiveness of repeated controlling the disease or hyperthyroidism persist, then the second doses of I-131 in cases of recurrence and metastasis. dose, third dose or fourth dose was given after 6 months interval In this study we had evaluated 24 DTC cases who were given 5 to with proper clinical and biochemical evaluation. If even with 13 doses of I-131 for ablation, recurrence and metastasis (in lymph fourth dose, hyperthyroidism was not controlled, the case was node, lung and bone). The ages of the patients were between 18 to referred for surgical management. The amount of radioiodine 70 years. These patients were given treatment in between 1982 to given in the second dose and in subsequent third dose or fourth 1993 and were followed up for 12-22 years. dose was same as first dose or higher. Early complications of It had been found that 6 cases out of 24 had bone metastases and all radioiodine were only encountered when the patient attended the were follicular type of carcinoma except one who had mixed type. centre for such. During follow up, patients were classified as cured Not one of these cases was found completely disease free. Two if the functional status was either euthyroid or hypothyroid within patients were found scan negative in two consecutive scans, but 1 year without further treatment of hyperthyroidism by antithyroid again became scan positive. One patient died 10 years after drugs or radioiodine. Patient was diagnosed as hypothyroid on the detection of carcinoma after given 9 doses of I-131; another basis of clinical and biochemical criteria, including low T4 and patient died 15 years after starting treatment with 13 doses. high TSH. Total 203 patients with hyperthyroidism treated with Another 2 patients had period of clinical improvement and radioiodine were studied. Among 203, 117 were female and 86 deterioration that also got more than 8 doses. were male with female male ratio of 1.4:1. The mean age of the There were 4 cases of lung metastases (4 out 24) and only one had patients was 38.38 10.42 years (ranged 16 years to 70years). papillary carcinoma. Lung metastases were cured in 2 cases after 5 Among 203 cases, 190 (172 Graves' diseases, 8 solitary toxic doses and was scan and Tg negative for 8 years; 2 cases of lung nodule, 10 toxic multinodular goiter) patients attended regularly metastasis were in good clinical state but still they some World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 22. S-16 Abstracts: ICRT-2005 recurrence even after having more than 8 doses. One of these Though radioiodine is supplied in a lead container, for treatment patients is surviving for 17 years after disease detection with scan purpose, it is administered after dispensing into a glass jar that positive state. does not adequately protect radiation hazards. For this reason, we Recurrence of diseases in thyroid bed have good prognosis but designed & developed a lead jar and radioiodine is dispensed into these patients sometimes needed more than 5 doses to get relieve that lead jar to minimize radiation hazards. For oral administration from recurrence. In our study among the 24 cases 6 patients of radioiodine to hyperthyroid patients, a lead jar was designed needed more than 5 doses. Radioactive iodine was also not so and developed with lead in Centre for Nuclear Medicine & effective in lymph node metastasis but surgical management is Ultrasound, Khulna in December 2004 by own expertise and successful in most cases technologies in such a way that a glass jar could be introduced into This study showed that bone metastasis has least curative effect by that lead jar. The thickness of lead was 4.04 mm and the thickness I-131 and prognosis is worst. However, I-131 can still prolong life of glass jar was 0.7 mm and thus the whole thickness of lead jar and it has also palliative effects in metastatic bone disease. became 4.74 mm. The desired dose of radioiodine (8 mCi) that should be given to the patients were dispensed into that lead jar 009-BGD and administered orally to the patients. Radiation levels in 10 such Targeted Therapy of neuroblastoma with I-131 MIBG: cases were measured by Mini-Rad Series-1000 survey meter at 0.5 Experience in 15 Cases. meter, 1 meter and 3 meters distances both lead jar and glass jar. Hussain R, Nisa L, Karim MA The mean radiation level of lead jar and glass jar during oral Institute of Nuclear Medicine & Ultrasound, BSMMU, Dhaka, administration of 8 mCi of Na131I solution in 10 cases at 0.5 meter, Bangladesh; Centre for Nuclear Medicine & Ultrasound, Mitford, 1 meter and 3 meters distances were 62.4± 1.96 microSv/h, 17.7± Dhaka, Bangladesh; Director, Bio-Sciences Division, BAEC, 1.95 microSv/h, 3.39± .12 microSv/h and 20.3± 2.16 microSv/h, Dhaka, Bangladesh 79.8 ± 0.79 microSv/h, 1.97 ± 0.23 microSv/h respectively. We have found that radiation level reduced by 67.47%, 61.58%, and I-131 MIBG has been proven to be an effective therapeutic option 41.89% with lead jar at 0.5 meter, 1 meter and 3 meters distances. in neuroblastoma targeted both at the primary tumor and its distant In conclusion, the locally designed and developed lead jar is safe, metastasis. We describe our initial experience in the targeted easy to handle and reduces radiation burden significantly in oral treatment of 15 patients with neuroblastoma. The patients were administration of radioiodine to hyperthyroid patients and grouped and treated according to three protocols. Group 1: recommended for routine practices in all nuclear medicine patients were in the advanced stage of the disease with either establishments. metastatic or unresectable disease; Group II: patients were treated immediately after diagnosis before surgery or any other 011-BGD management. Group III patients were treated with combined I-131 Radioiodine Treatment for Complicated Hyperthyroidism MIBG and high dose chemotherapy. The method of Using a Fixed Dose Regime administration was by slow infusion (120min). Dose varied from 4 Paul AK, Rahman SH, Ansari SM Centre for Nuclear Medicine to 12 GBq in a single dose. All patients were followed up with and Ultrasound, Khulna, Bangladesh periodic blood counts, liver and kidney function tests, thyroid and Centre for Nuclear Medicine and Ultrasound, Bogra, Bangladesh adrenal function tests. The response rate in group-I was 38%, group-II patients showed 52% and in group-III the overall Hyperthyroidism in the elderly and all those with cardiovascular response rate was 72.6%. Responses depended on high tumoral I- and psychiatric problem has increased mortality and morbidity 131 MIBG uptake and limited spread of the neoplasm. As regards rate. These patients need special care to cure the disease promptly toxicity, the major side effect observed was myelosuppression and and permanently for avoidance of complications. Radioactive I- this was found to be more severe in patients with bone marrow 131 is one of the accepted forms of treatment for hyperthyroidism involvement and after chemotherapy. Toxicity was relatively mild and increasingly being considered for the patients in whom rapid in the neuroblastoma patients who were treated at diagnosis. There and permanent control of disease is desirable. To evaluate the was no incidence of serious infections or significant bleeding in success of I-131 to cure disease in-patients with complicated any of our patients. Extramedullary toxicity of hypothyroidism hyperthyroidism, we prospectively studied the outcome of was observed in 1 patient. On the basis of the results, we can radioiodine therapy using a fixed dose regime. Ninety-three conclude that MIBG is an excellent pharmaceutical for the patients with toxic diffuse goitre (65 female, 28 male) age ranging delivery of therapeutic doses of radioiodine for neuroblastoma. from 29-67 years (mean ? SD 41.35 ? 11.02 years) were evaluated. When combined with chemotherapy it is effective in obtaining a The subjects included 71 cases with cardiovascular problem, 13 rapid response in heavily pre-treated patients who are resistant to elderly patients, 5 with poor drug compliance and 4 with other therapies. associated psychiatric disease. The individual was excluded from the study who had autonomous toxic nodule. Every patient was 010-BGD pretreated with antithyroid drugs for 4 weeks and the drug was Design & Development of a Lead Jar For Oral discontinued for 3 days before administering I-131. No patients Administration of Radioiodine In Hyperthyroid Patients. had post-treatment antithyroid drugs. All the patients were treated Rahman MS, Paul AK, Rahman HA, Begum F. Centre for Nuclear with a fixed oral dose of 15 mCi I-131 sodium iodide. Post- Medicine & Ultrasound, Khulna, Bangladesh treatment follow-up examinations were done at 6 weeks without biochemical tests, at 3 months, 6 months, 9 months and 1 year and Nuclear Medicine practices involve use of radioisotopes for then annually with biochemical tests. Patients were classified as diagnosis and treatment of diseases. Radioiodine is one of such cured if the biochemical status was either euthyroid or radioisotopes, being used in the diagnosis and treatment of hypothyroid at one year without further treatment by antithyroid diseases since 1942. Handling of radioiodine involves radiation drugs or radioiodine. Of the 93 cases, 82 patients became hazards both for the patients as well as for the technologists. euthyroid or hypothyroid requiring no further treatment for World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 23. S-17 Abstracts: ICRT-2005 hyperthyroidism with an overall cure of 88.17%. Hypothyroidism Ultrasound, Dhaka. The patients were referred by the eye surgeons was developed in 49 (52.69%) patients at one year of whom 39 soon after excision of the lesion for beta radiation to the affected became hypothyroid within 6 months and another 10 patients area. Hand held Sr-90 contact applicator from Amersham within 1 year. 4 patients were subclinical hyperthyroid at 6 months International was used to deliver a total dose of 2500 cGy radiation and still hyperthyroid at 9 months. 7 patients remained to the sclera surface in five fractions. Care was taken to anesthetize hyperthyroid 6 months after treatment. Thus, 11 (11.83%) patients the eye(s) before each application. The patients were then remaining hyperthyroid 6 months following I-131 treatment and followed up at one week, one month, six months and one-year they were treated with a 2nd dose of 15 mCi I-131. No patient interval after beta irradiation. The age range of the patients required more than two doses of I-131 in this study. In conclusion suffering from primary pterygium was 18 to 40 years. All patients an initial dose15 mCi of I-131 is a simple, safe and effective means underwent surgical excision with bare sclera technique. Of the for the treatment of patient with complicated hyperthyroidism. patients treated 42 patients were completely lost to follow up, while 28 patients were followed up at different periods for up to 12 012-BGD months. In these patients the local control rate of pterygium after Use of Strontium-90 Beta Irradiation as an Adjunctive irradiation was 94.6% after 12 months. Recurrence of the Therapy For The Management of Squamous Cell Carcinoma pterygium occurred in 5.4% of cases who were given a second of The Conjunctiva. course of strontium therapy. Follow- up after six months showed Nisa L , Momta S , Jehan AH, Rahman MU these patients to remain free of the disease. Associated Center for Nuclear Medicine & Ultrasound, Mitford Hospital complications were mild and included conjunctivitis. There was Campus, Dhaka. improvement of visual acuity in 21 patients with no evidence of cataract or ulceration noted in any of 28 patients during the 12- To evaluate the effectiveness of strontium-90 beta irradiation in month follow-up period. In conclusion, beta irradiation with Sr-90 management of squamous cell carcinoma of the conjunctiva. A after surgical excision of pterygium was found to be a safe a nd retrospective analysis of the medical records of 5 patients treated cost- effective means of controlling the recurrence rate of with strontium-90 beta irradiation was done. Squamous cell pterygium. carcinoma of the conjunctiva was histologically proved in all patients who had initial surgery to remove the major part of the 014-BGD lesion. This was followed by beta radiation within 48 hours with Sr Second Malignancies Following The Treatment of -90 contact applicator obtained from Amersham International. Differentiated Thyroid Carcinoma With Radioiodine The hand held Sr- 90 eye applicator was used after appropriately Yasmin, S, Nisa L, Haque FS, Begum R. Institute of Nuclear instilling the eyes with local anesthetics and a total of 5000cGy Medicine & Ultrasound, Dhaka was delivered in seven fractions. Follow-up period was from 6 to Center for Nuclear Medicine & Ultrasound, Mitford Hospital, 12months. Clinical response and side effects to the therapy were Dhaka. used as outcome measurements. Three patients showed good response with no evidence of tumor within 6 to 12 months of the To see the incidence of second cancers in patients with well follow-up period. One patient was lost to follow-up and one differentiated thyroid carcinoma after being treated with patient showed local recurrence within 4 months. In this patient radioiodine. Medical records of 814 (417males, 397females) the tumor was more extensive involving the limbal conjunctiva patients with differentiated thyroid cancer treated at Institute of and the cornea. Nuclear Medicine & Ultrasound, Dhaka were reviewed. The The early side effects of beta radiation reported by all five patients purpose was to investigate the incidence of second cancer in these were temporary local irritation of the eyes with additional mild patients after radioiodine therapy. The age range of the patient chemosis in four patients. None of the other three potentially cured population treated with radioiodine was 9 to 69 years. Doses of patients showed any long-term adverse reactions. There were no radioiodine given were in the range of 30 to 100mCi for ablation incidence of late radiation induced complications such as corneal and 150 to 250mCi for treatment of metastasis. The median ulcerations, damage to cornea, eye pain, cataract or any other follow-up period was 93.7± 15months. Eleven (1.35 %) of the 814 serious effects in these patients within the follow-up period. In patients developed a second malignancy. Two patients (0.25%) conclusion, beta irradiation is an effective post-surgical therapy developed chronic myelogenous leukemia within a latency period for local control of superficial conjunctival squamous cell of 5years and after receiving a cumulative dose of 600- 670mCi. carcinoma. The very low and minimum side -effects of Sr-90 The over all incidence of second malignancy in the form of solid irradiation is an advantage, which makes it a good alternative to tumors was 1.10%. Of the nine patients with solid tumors, there external beam radiation, which has serious side effects. were two patients with renal cell carcinoma, three patients with parotid gland tumor, one patient with pancreatic cancer, one with 013-BGD adenocarcinoma of the stomach, one with carcinoid tumor and one Post-Operative Beta-Irradiation in The Management of with small cell carcinoma of the lungs. The mean latency period Pterygium for development of these tumors was 6.92 ± 3.934 years and the Jehan AH, Nisa L, Hossain R, Yasmeen S, Karim MA mean cumulative dose received by all these patients was 537.25± Center for Nuclear Medicine & Ultrasound, Mitford; Institute of 120.55 mCi. Follow-up of a fairly large cohort of patients treated Nuclear Medicine & Ultrasound; Director, Bio-Science Division, with radioiodine showed a low incidence of second neoplasm. No BAEC. relation was observed between the cumulative dose received and the development of a second malignancy. Thyroid carcinoma is a A retrospective analysis of the effectiveness of Sr-90 therapy in polygenic disease, which may be associated with other post-operative management of pterygium. Between June 1999 malignancies. Common environmental or genetic factors as well and May 2001 a total of 70 patients received beta radiation for as long-term carcinogenic effects of radioiodine therapy should be treatment of pterygium at the Institute of Nuclear Medicine & considered. World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 24. S-18 Abstracts: ICRT-2005 015-BRA Most of neuroendocrine tumors (NT) and a few others have an Use of Samarium 153 Hydroxyapatite for intra-articular over-expression of somatostatin receptors in their cellular surface therapy allowing “in vivo” detection of both primary tumors and its Anselmi OE metastasis by diagnostic scintigraphic images with Octreotide labeled with 111In. Patients with inoperable, residual or metastatic Abstract not received NE tumors have typically a poor response to conventional radiotherapy or chemotherapy. A new valid option for therapeutic 016-BUL purposes in such cases is the use of a similar peptide like DOTA- Tc-99m MIBI and I-131 scintigraphy in the follow-up of D-Phe-Tyr-Octreotide labeled with Yttrium-90 (90Y-DOTATOC). differentiated thyroid carcinoma (DTC) patients after surgery This radiopharmaceutical is a pure beta emitter with specific Sergieva S, Hadjieva T, Botev V, Dudov A. Sofia Cancer Center, affinity for subtype 2 somatostatin receptors allowing a high UH “Queen Joanna”, Sofia, Bulgaria radiation dose to cellular level in NT. With the strong collaboration of the European Institute of Oncology, Milan MIBI scan has been reported to be a highly sensitive imaging (Italy), we have successfully incorporated this therapy in Chile technique for detection of differentiated thyroid carcinoma (DTC) including both the local labeling of the radiopharmaceutical and metastases that have lost the capability to take up I-131. The the design of the clinical protocols. purpose of the present study was to evaluate retrospectively the We have treated 23 patients, 11 men and 12 women (average 46.6 value of the Tc-99m MIBI scan and I-131 whole body scintigraphy y.o. range 12-70), 22 with histologically confirmed residual or using thyroglobulin (Tg) levels as a basis for comparison. Eighty metastatic NT and 1 hepatoma. All of them had positive four patients (63F/21M) with an age range of 17-74 yrs (mean age somatostatin receptors demonstrated by 111In-Octreotide = 43.5 yr) of DTC (47 cases with papillary, 18 cases with follicular scintigraphy. The primary tumor was pancreatic (10), intestinal and 19 cases with mixed papillary-follicular ) were assessed. All (5), medullary thyroid carcinoma (2), thymus (1), bronchial (1) of them had undergone total or near-total thyroidectomy and and unknown origin (3). All patients received renal protection received radioiodine treatment for ablation of post surgical with crystalline amino acids immediately before the residual thyroid tissue. They were examined after L-thyroxin radiopharmaceutical administration. The 90Y-DOTATOC, labeled withdrawal over 4-5 weeks during the follow-up period. Planar at CGM Nuclear in Santiago with 90Y from MDS Nordion and whole body images were acquired at 15 min and 180 min after (Canada) and peptides from Pichem (Austria), was administered i.v. administration of Tc-99m MIBI (555-740 MBq) and at 48 intravenously in single doses between 25-240 mCi (maximum hours after p.o. administration of I-131 (111-185 MBq) on Toshiba total individual dose of 537 mCi). The whole group received 66 GCA gamma camera. Serum Tg assays were performed to clarify single therapy doses. Until now 16 patients have received more the presence of residual recurrent malignancy. All scintigraphic than one dose, 2 doses in 6, 3 in 2, 4 in 2, 5 in 4, 6 in 1 and 7 in 1. findings were compared with US, CT or MRT data. I-131 scans Only this sub-group is considered for evaluation of treatment were positive in 55 patients showing thyroid remnants in 31 cases, response. Radiochemical controls were done in minicolumns lymph node metastases in 24 cases (17 in the neck, 7 to Sep-Pak C18 previously to the patient injections. neck/mediastinum), pulmonary metastases in 6 cases and bone Radiochemical control showed a labeling efficiency of the lesions in 2 cases. In 18 patients I-131 scans were negative and Tg radiopharmaceutical higher than 99%. In 16 patients with more levels were undetectable, so patients were considered tumor-free. than one cycle there has been complete remission of the tumor In 11 patients I-131 scans were negative while serum Tg levels activity in 1, significant partial remission in 10, partial remission were increased. These false negative results were observed in 3 with further relapse and progression in 2. The treatment was predominantly in cases with less differentiated metastatic cells, well tolerated in all the patients except in one in whom by causes especially after several courses of high-dose I-131 therapy. Tc- not yet determined the “in vivo” biodistribution of DOTATOC 99m MIBI scans revealed the presence of lymph node and/or lung was altered showing mainly bone marrow uptake (non-tumor) of metastases (non-functioning metastases) in 9 of them, false 90 Y presenting a severe but reversible hematological toxicity. This negative results were obtained in 2 cases. Serum Tg was increased patient was considered non-treated since there was no selective in all patients with local lymph node and distant metastases, tumor irradiation. The other patients showed mild reversible visualized by I-131 or by Tc-99m MIBI, but also in 18 patients hematological toxicity. In a 36 y.o. female patient suffering a with thyroid remnants only. Considering I-131 scan as the most progressing pancreatic NT with multiple metastasis and severe specific standard procedure we may conclude that the combined bone marrow involvement presenting partial response and further Tc-99m MIBI scintigraphy and serum Tg assay appear to be an relapse, a high rescue dose of 240 mCi was administered alternate method for large dose I-131 scan for demonstrating the following a successful autologous stem cells transplantation. The extent of the disease in cases with DTC and elevated Tg. patient is now asymptomatic with significant partial response. These preliminary data indicate that the treatment with 90Y- 017-CHI DOTATOC, now available in Chile, is a valuable therapeutic Peptide Receptor Radionuclide Therapy With Y-90-Dotatoc option for these type tumors that frequently do not respond to (somatostatin Analog) in Neuroendocrine Tumours: The conventional treatments like chemotherapy or external Chilean Experience radiotherapy. Peptide receptor therapy should be considered as Amaral H1-2, Pruzzo R1, Morales B1, Gil C3, Coudeu I2, Rojas A1, first line treatment in well-differentiated NT. Majlis A1-2, Kleinman S1-2, Vogel C1-2, Rossi R1, de la Fuente H2, Reyes C2, Varas M1, Chinol M4 and Paganelli G4 1 Clinica Alemana, 2Fundacion A. Lopez Perez, 3CGM Nuclear, Santiago (Chile) and 4European Institute of Oncology, Milan (Italy). World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 25. S-19 Abstracts: ICRT-2005 018-COL for the treatment of liver cancer, I-131 Lipiodol, has been found to Re-188 Lipiodol Therapy of Hepatocellular Carcinoma be prohibitively expensive, and it is virtually not practical to use Bernal P, Chau T, Erdenechimeg S, Kumar A, Srivastava D, this radiopharceutical on a routine basis in the poor and Pusuwan P, Ang S, Barrenechea EA, Jeong JM, Onkhuudai P, developing countries of the world. In the year 2001 the IAEA Knapp FF, Sundram FX, Divgi C, Buscombe J, Dondi M, Padhy started a new coordinated research in order to identify and test a AK. (Based on the results of an International multi-centric study new cost-effective radiopharmaceutical for the treatment of liver initiated by the IAEA) cancer. With the help of scientists for Korea, Singapore and USA it has been possible to label Rhenium 188 with Lipiodol which has Hepatocellular carcinoma (HCC) is a malignant epithelial tumour shown excellent concentration in the HCC when administered arising from parenchymatous liver cells. It is one of the world's trans-arterially. Phase-1 study revealed that the right quantity of most common malignancies, causing almost one million deaths the radioconjugate can be delivered after 'scout' dose dosimetry annually. About 315,000 new cases of HCC are reported per year studies have been done, to spare normal liver and lung from excess which constitutes 5.6% of all cancers among males and 2.7% of all radiation dose. The phase-1 data showed that the treatment is safe cancers among females. Control strategies to prevent occurrence with minimal side-effects, at a dose up to about 200 mCi of Re-188 of HCC are sub-optimal; this is evident by the rising incidence of lipiodol. The Phase-2 study in over 100 patients revealed HCC even in developed nations like the USA, where the excellent results. With a median follow-up time of 449 days, the prevalence of the disease is one of the lowest in the world. results have demonstrated one-year survival rate of 56%, while at Currently, patients with HCC have an extremely poor prognosis the time of the analysis (which was almost two years after with a five year survival rate of less than 5% . However, morbidity treatment for some patients) the survival rate was found to be 40%; and mortality in such patients are not determined by the presence which is remarkable keeping in view the types of patients of HCC alone, but are also influenced by the activity of the recruited, most of who were end-stage disease. underlying liver disease, as well as the functional status of the liver. The stage of the tumor (size, number, vascular invasion, 019-CPR extra hepatic spread) has been consistently documented to be an Retinoic Acid in Patients with Radioiodine Non-Responsive important determinant of the natural course of the disease. These Differentiated Thyroid Carcinoma. factors are major variables that influence various therapeutic Zheng R, Zhang W, Li J, Chen S. Department of Nuclear strategies directed against this tumor in recent times. Therefore, Medicine, Cancer Hospital and Institute, Chinese Academy of therapy in HCC needs to be optimized depending upon the above Medical Sciences, Beijing 100021, P. R. China mentioned influences on the final outcome of the disease. Various forms of therapy such as surgical resection, orthotopic For the treatment of differentiated thyroid cancer, surgery, liver transplantation (OLT), percutaneous injection to induce radioiodide therapy, and thyrotropin-suppressive thyroxine coagulative necrosis of the tumor using agents like ethanol, acetic application represent established therapeutic measures of proven acid, hot saline, microwave and laser have been considered as efficiency, affording a good prognosis for this disease. However, radical treatment of HCC, aiming at curing the disease. The in up to 30% of the cases, de-differentiation is observed, giving understanding of pathology, pathogenesis, natural course and risk rise to tumours that are refractory to conventional treatment. factors of HCC during the last three decades has resulted in the Experimental data shows strong evidence that differentiated development of multiple therapeutic approaches with promising functions of iodine metabolism can be re-induced by retinoic acids yet varying results. (RA). The aim of our study was to assess the effects of retinoic acid Most patients with hepatoma from the developing countries at the therapy in patients with extensive thyroid tumor involvement, time of their presentation to the doctor fall into the which lost radioiodine uptake ability. Twenty-five patients who intermediate/inoperable category , and for these, radionuclide received retinoic acid therapy between Feb. 1999 to Dec. 2004 methods to deliver high radiation doses to tumor must be were reviewed retrospectively. There were 15 males and 10 considered. Uncontrolled studies using radioisotopes like I-131, females with a mean age of 52.5 years (16-71 years). Most of them Y-90, Ho-166, Re-186 conjugated to monoclonal antibodies, underwent total or near total thyroidectomy before I- lipiodol or chemical compounds have shown promising results. 131treatment. Twenty-one patients were papillary carcinoma and However due to lack of prospectively designed randomised trials, four were follicular carcinoma. Twenty-two patients had lung their efficacy is yet to be optimally evaluated. There has also been metastasis and three had bone metastasis. Thyroid hormone reports (from one study only) on the usefulness of radionuclide medications were withdrawn for two weeks in case of therapy as an adjuvant treatment following resection of “curable” triiodothyronine (T3) and five weeks in case of thyroxine (T4). HCC. It has been shown that patients given a single administration For treatment of bone metastases, an amount of 7.4 GBq (200mCi) of 1GBq. Of I-131 Lipiodol have significantly greater survival and of I-131 was given every six months. For treatment of pulmonary less recurrence than those not treated. It is important that the metastases an amount of 5.55-7.4 GBq (150-200mCi) was given results of this study be verified and confirmed by reproducing the every six months. In 25 patients with advanced thyroid cancer, results in another prospective trial. whose cancer foci did not concentrate radioiodine, retinoic acid It may be noted that the disease is most prevalent in those was given for 6 weeks before radioiodine treatment, followed by I- communities with least resources for setting up clinical trials. 131 treatment. All patients had I-131 scans and thyroglobulin Hence the role of the International Organizations like IAEA and measurements 7 days after administration of I-131. X-ray, bone WHO are extremely important in assisting them in setting up such scan, and ultrasound of the neck were done one month after trials and coordinating them. For nuclear medicine and the IAEA- administration of I-131. One patient received RA therapy four WHO to develop a key role in the treatment of HCC, new methods times and two patients received RA twice. In the post-therapy must be evolved, tested and standardized in full random controlled radioiodine scans, radioiodine uptake was noted in 9 patients with trials. lung metastases and in 2 patients with bone metastases. On the Currently the only commercially available radiopharmaceutical whole, in 44% (11/25) of patients re-induction of radioiodine World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 26. S-20 Abstracts: ICRT-2005 uptake was observed. Levels of thyroglobulin concentration calculating dose was 11.08%?44.03 MBq. The biggest different before and after RA therapy did not differ significantly (P>0.05). value was 44.26% and 446.59 MBq, respectively. To sum up, the In our study, all patients completed the treatment and the most dose and the therapeutic effect had a significant difference in the frequent side effects were fatigue. Dry skin, mouth and lips different period of the years although the therapeutic method and occurred in 35% of patients. Most side effects were well tolerated the calculating formula was the same. Therefore, the scientific and by the patients and reversible following cessation of RA therapy. feasible function of the “Quimby” formula should be considered We conclude that retinoic acid can induce radioiodine uptake and deeply. Moreover, the uptake rate of I-131 was changed the side effects are well tolerated. However, prospective studies in significantly in a short period. In order to solve these problems, on larger groups of patients are necessary to prove its clinical utility the basis of our experience, according to the individual sensitivity in routine practice. and the exceeding dose were the main causes of the incidence of the hypothyroidism, we put forward to simplify the therapeutic 020-CPR method. We suggested to choose the thyroid weight as the only Study of the Therapeutic Dose and the Clinical Effect on factor-thyroid weight times a fixed coefficient, to take into Graves’ Disease With I-131 Treatment consideration the patient’s clinical condition and to choose the Y. Dang. Imaging Diagnostic Center of Nanfang Hospital, dose within the range of 111-222 MBq or 2.59-4.07MBq/g as a Southern Medical University, Guangzhou, China suitable optimal dose for therapy. Graves’ disease is being treated with I-131 for more than 40 years 021-CZR in China. Previously the dose of I-131 used to be calculated using Our Experience With Radioiodine Therapy of Thyroid the “Quimby” formula. We have now observed that the dose of I- Functional Autonomies 131 administered to patients is now lower in recent years than the Otakar Kraft. Department of Nuclear Medicine, University early years. The radioactive iodine uptake by the thyroid gland has Hospital, Ostrava-Poruba, Czech Republic also changed significantly over a period of time. In this paper we intend to explore these reasons and to research the relationship In this paper the author presents his experience with radioiodine between the dose and the effect as well as the main cause of the therapy of thyroid functional autonomies. The objectives of this incidence of the hypothyroidism. The parameters in “Quimby” study were to establish the efficacy and determine the adverse formula including I-131 uptake, effective half-life and thyroid effects of radioiodine therapy of patients with thyroid functional weight were analyzed and compared with each year data from autonomies. 1961 to 1988 and subjected to multiple regression analysis to The main pathologic attribute of thyroid functional autonomies is determine the influence on the calculation of dose in 4465 the loss of regulation in the axis of hypothalamus-hypophysis- patients. The therapeutic effects were compared with the data of thyroid. The main cause of functional autonomy of the thyroid is the clinical follow-up of patients between 1961-1973 and 1978- iodine deficiency. Over a period of 30 years (1974-2004) 799 1988 in 748 patients. The factors which might lead to the patients (age from 33 to 86 years; average age 58.7 years; the hypothyroidism were investigated with the non-condition logistic female: male ration was 7.4:1) with unifocal functional autonomy regression. The I-131 uptake was repeatedly measured within one (UFA), multifocal functional autonomy (MFA) and disseminated week in 100 patients to identify the changing pattern of the I-131 functional autonomy (DFA) received at least one treatment of uptake and its influence on the administered therapeutic dose. We radioiodine. For diagnostics and the evaluation of radioiodine observed an increase in the value of I-131 uptake. The value of I- therapeutic effect of functional autonomies a thyroid scintigraphy 131 uptake showed an increase after 1977, as well as a is the basic and necessary procedure. In some patients a common prolongation of effective half-life after 1973. The main reason for scintigraphy with special imaging modulation, in some patients a these changes being a replacement of the equipment in 1977 (G-M scintigraphy after suppression or stimulation by means of thyroid counter tube was replaced by scintillation counter), and the other hormones or TSH were done. We have also performed a thyroid reason being salt iodization in China in 1973. These two factors ultrasonography, an assessment of a serum level of a total and free resulted in a significant reduction in the administered dose of I- thyroxine, total triiodothyronine, TSH, radioiodine accumulation 131 during the period 1974-1988 as compared to the previous test, estimation of radioiodine effective half-life, in some patients period 1961-1973; the mean administered doses being TRH-TSH test. The follow-up examinations were done in all 168.35MBq and 330.33MBq respectively. The result of multiple patients after 4-6 months, another examination after one year in regression analyses suggested that the thyroid weight and the 545 patients and after two years in 254 patients. One therapeutic effective half-life were the most important factors to influence on dose received 733 patients (91.74%) and it was sufficient for an the dose calculation. The therapeutic effects demonstrated that it elimination of functional autonomies. Some patients were re- was significantly different between 1961-1973 and 1978-1988. treated if there was the evidence of small or no treatment effect and The incidence of hypothyroidism in 1961-1973 was obviously no elimination of functional autonomies. Two radioiodine higher (58.58%) than in 1978-1988(19.01%). The non-condition treatments received 62 patients (7.76%) and three treatments 4 logistic regression of the factors which lead to the hypothyroidism patients (0.5%). We advocate individual pre-therapeutic were analysed, which showed that the individual sensitivity and dosimetry to determine the activity necessary to achieve a targeted the higher administered doses were the main causes of radiation dose in autonomously functioning tissue. The hypothyroidism. The data also showed that the results were highly radioiodine amount administered was based on the volume of satisfactory when the administered doses were within 111- thyroid or the nodule, 24-hours radioiodine accumulation, the 222MBq or 2.59-4.07MBq/g. The coefficients of variation (CV) effective half-life of radioiodine, the absorbed dose of 500 Gy per of the mean value of the two peak I-131 uptake values determined gram of the nodule (UFA) or 300 Gy per gram of the whole thyroid within one week in 100 patients was12.78. The biggest CV was (in patients with MFA and DFA). 61.42%. There were 41% patients with CV=10%. The absolute Before radioiodine therapy an average serum levels of total difference mean value of the two peak I-131 uptake rate and thyroxine was 164.6 nmol/l, of free thyroxine 20.8 pmol/l and World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 27. S-21 Abstracts: ICRT-2005 triiodothyronine 3.2 nmol/l, in all patients TSH was suppressed. after 1 year in 43% the swelling and the filling reduction and in Before therapy patient's complaints were cardiovascular in 88% of 61% the pain reduction, after 2 yrs in 35% the swelling and the patients (tachycardia, irregular pulse, palpitation), neurological filling reduction and in 51% the pain reduction. (nerves, agitation) in 72% of patients, hypermetabolic (loss of After RSO we have observed a significant reduction of blood pool weight, intolerance of warm, perspiration) in 68% of patients and activity and synovial swelling with further improvement in the local (feeling of neck compression, swallow difficulties) in 30% following months. There is a strong correlation between the of patients. reduction of blood pool activity (apparent on TPBS), synovial After therapy the average serum levels of total thyroxine was swelling (apparent on USG) and improvement of pain. 108.8 nmol/l, free thyroxine 12.5 pmol/l and triiodothyronine 2.0 Ultrasonography finding: nmol/l and improvement of symptoms in 91%, without Single RSO: before therapy: marked filling and synovial reaction improvement in 8.7% and worsening in 0.3% of patients. The with villus; after 6 months, 1 year and 2 years: without treatment suppression of TSH disappeared in 607 of treated patients (76%). effect - the same ultrasonographic finding; partial effect - the A volume reduction of thyroid of 38% was achieved in any type of reduction of the filling, synovial villus and synovitis have not functional autonomy after radioiodine treatment. Side effects diffuse character; substantial effect minimal filling without were minimal and in some patients presented as a transient neck synovial reaction. pressure or pain and neck swelling as a manifestation of post Re-RSO: before therapy: marked filling and synovial reaction radiation thyroiditis. Post radiation hypothyroidism was with villus; after 6 months, 1 year and 2 years: without treatment diagnosed in 36 patients (4.5%). The results of this study show that effect - similar ultrasonographic finding as before treatment with the radioiodine therapy of the thyroid functional autonomies is some ligamentous reaction; partial effect - the reduction of the safe, with low incidence of adverse effects. It is effective and for filling, synovial villus and the synovitis have not diffuse character patients non-demanding. with synovial ligamentous reaction; substantial effect - without filling and minimal synovial reaction with sporadic occurrence of 022-CZR synovial villus, synovial ligamentous reaction. Our Experience With Radiosynoviorthesis and Re- Radiographic finding: Radiosynoviorthesis of Knees Before therapy it depends on the primary diagnosis. After single 1 Otakar Kraft, 2Richard Kaspsrek RSO: without therapeutic effect - after 6 months: it does not 1 Department of Nuclear Medicine and 2 Department of change or it impairs; after 1 and 2 years: it impairs; partial Orthopaedics, University Hospital, Ostrava-Poruba, Czech treatment effect: after 6 months: it does not change, after 1 and 2 Republic years: it does not change or it can impair; substantial efect: after 6 month, 1 and 2 years: radiographic finding does not impair, it does In this paper the authors present their experience with not change. radiosynoviorthesis (RSO) and re-radiosynoviorthesis (re-RSO) After re-RSO: entirely the same radiographic finding as after of knees. The objectives of this study were to compare treatment single RSO. results between first RSO and re-RSO. TPBS: The finding before single RSO and re-RSO: positive the Before RSO an ultrasonography (USG), an X-ray, a three-phase first two phases of TPBS. bone scintigraphy (TPBS). The treatment effect (TE) can be After single RSO: without therapeutic effect - after 6 months, 1 expected if a synovitis is proved by these examinations. and 2 years: it does not change with higher bood pool, partial To knees we inject 200 MBq of the yttrium citrate. TE is evaluated treatment effect: after 6 months, 1 and 2 years: blood pool can be by the clinical examination, USG and TPBS. If the effect of RSO is higher but not so much as before treatment; substantial efect: after not satisfying, RSO can be repeated no sooner than 6 months later. 6 month, 1 and 2 years: normalization of blood pool. Among our patients we have high percentage of re-RSO. A rate After re-RSO: entirely the same blood-pool finding as after single between single RSO and re-RSO was 11:8. RSO. From 1986 to December 2004 we treated 1267 knees with Yttrium We have observed side effects of the therapy in 5% patients in the Citrate 37.9% patients had gonarthrosis, 26.1% chronic form of a radiation synovitis which has subsided after 2 or 3 weeks synovitis, 20.3% revmatoid arthritis, 4.6% relapsing fluid, 3.9% during combined symptomatic therapy with antirevmatics, psoriatic arthropathy, 3.3% ankylozing spondylarthritis and 1.3% orthesis and subsequent rehabilitation. hemophilic arthropathy. RSO is effective, simple and for patients the convenient treatment The evaluation of TE by patients in 294 RSO (170 patients with procedure with a low occurrence of undesirable effects. Repeated single RSO and 124 pts with re-RSO an influence on a pain and a RSO were as effective as single RSO, and its repeated use does not fluid formation after single RSO: 10.9% no influence, 42.2% decrease the expected TE. substantial and long-term effect, 46.9% partial TE and after re- RSO: 8.2% no influence, 36.6% the substantial and long-term TE, 023-CZR 55,2% the partial TE. The best results evaluated by patients were International Cooperation in the Treatment of Patients with in patients with the revmatoid arthritis and heamophilia. Worst Differentiated Thyroid Cancers 1 results were in osteoarthritis in case of considerable radiological Otakar Kraft, 2Ivan Reznak 1 changes. Department of Nuclear Medicine, University Hospital, Ostrava- Clinical follow up of 110 pts with single RSO and 70 pts with re- Poruba, Czech Republic 2 RSO: after single RSO: after 6 months in 77% swelling and a Department of Nuclear Medicine, University Hospital, Martin, filling reduction and in 86% pain reduction, after 1 year in 53% the Slovak Republic swelling and the filling reduction and in 62% the pain reduction, after 2 yrs in 28% the swelling and the filling reduction and in 48% In this paper we present our experience with the cooperation in the the pain reduction; after re-RSO: after 6 months in 62% the treatment of Slovak patients with differentiated thyroid cancers in swelling and the filling reduction and in 75% the pain reduction, Slovak and Czech hospitals. The treatment capacities in the World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 28. S-22 Abstracts: ICRT-2005 Slovak nuclear medicine departments are not sufficient for interview. Two of these Nuclear Medicine Centers are radioiodine therapy of patients with differentiated thyroid cancers Department of a Cancer Center and they have many patients for and that is why these patients are sent for this therapy to Czech therapies. In the majority opinion of Physicians, Cost of nuclear medicine departments. The objectives of this study were Radiopharmaceuticals is principal problem to use Therapy in to demonstrate the way of this cooperation and the results of Dominican Republic. In addition the following problems were therapy. We concentrated on the collaboration between the identified: Lack of awareness about new therapy in Nuclear Department of Nuclear Medicine in Martin in the Slovak Republic Medicine among Physicians of other specialties, lack of adequate and the Department of Nuclear Medicine in Ostrava, the Czech training in the current trends of radionuclide therapy and finally Republic. From 1991 to 2005 hundreds patients with lack of basic infrastructure, equipment and finances to buy differentiated thyroid cancers (follicular, papillary) underwent a radiopharmaceuticals and introduce radionuclide therapy. For this complex therapy. In Slovak hospitals they were diagnosed and reason, Nuclear Medicine Centers prefer to work with only I-131 operated on for the cancer (near-total thyroidectomy and removal Therapy and they do not have new programs to start other of lymph node metastases). Then they were sent to the Department therapies. In the near future, our deparment of Nuclear Medicine of Nuclear Medicine in Ostrava in the Czech Republic. In this will work with I-131, pain palliation, treatment of metastatic department a radioiodine ablation of thyroid remnants by means disease and Treatment of benign diseases. We have interest in of the treatment dose of radioiodine of a standard activity of 3,7 offering other therapies in the department and we hope that other GBq was performed and then a suppression and substitution departments with more resources, have the same interest, to therapy of thyroid hormones were started. After 3-6 months some enhance practice of radionuclide therapy in our Country. patients were examined by means of the diagnostic whole body scintigraphy after application of 300 MBq 131I. Some patients were 025-EGY treated by means of a standard activity of 7,4 GBq 131I and after 5 Osteosarcoma Target Therapy With Stem Cell Transplant: A days the whole body scintigraphy (WBS) was performed. In these Case Review both groups of patients the diagnostic or therapeutic radioiodine Fawzy A. application were done after withdrawal of thyroid hormone Nuclear Medicine unit, Faculty of Medicine, Cairo University, treatment. If thyroglobulin levels were low and WBSs were Egypt. negative, patients were followed up in the Department of Nuclear Medicine in Martin. Patients with radioiodine accumulated Radioisotopes with medium-energy beta emission and half life of metastases were again treated with radioiodine in Ostrava. If a few days are attractive option for systemic delivery of targeted indicated, the external radiation therapy targeted on the neck and irradiation. Samarium-153 ethylene diamine tetra-ethylene upper mediastinum was performed in the Slovak Republic, in phosphonale (153Sm-EDTMP), a bone-seeking radio- University Hospital in Martin. Newly formed lymph nodes pharmaceutical, provides therapeutic irradiation to osteoblastic metastases were surgically treated in Slovakia, too. In this paper osseous lesion. The usual dose of Sm-153 in metastatic disease is we analyze the treatment results in various groups in men, in 1mCi/Kg (37MBq/Kg) and the dose limiting toxicity is women, in patients with follicular cancers, in patients with thrombocytopenia. As local radiotherapy has only a limited papillary cancers, in younger and older patients. We also present therapeutic role in the treatment of osteosarcoma, and some types some interesting case reports. Generally we have very good of the tumour portray an unpredictable response to chemotherapy. treatment results with very low five years mortality. Also High dose Sm-153 (30mCi/Kg) was proposed for the target economically our partnership is cost effective. Our collaboration management of recurrent osteosarcoma, this was followed by successfully continues also after entrance of the Slovak Republic stem cell transplant (peripheral-blood progenitor, PBPCs). and the Czech Republic to the European Union in 2004. The A female child, 10 years old, with polyostotic osteosarcoma with results of this multi-center study show that international Czech local recurrence in the right hipbone was chosen for therapy. She and Slovak cooperation in the complex therapy of patients with had left knee prosthesis, right lower limb disarticulation, and was differentiated thyroid cancers is successful, with high efficacy. given chemotherapy in multiple regions. She was subjected to The treatment results are very good. MDP bone scan showing active uptake in an expanding bone lesion in the right hip bone, and was also subjected to MIBI scan, 024-DOM which showed negative uptake. Radiopharmaceutical Therapy in Dominican Republic. She received 30mCi/Kg Sm-153 (660mCi in total dose), with no Present and Future major events occurring in the post-injection period. After 10 days Johny Osvaldo de los Santos, M.D. the patient went into pancytopenia, which necessitated Department of Nuclear Medicine, Instituto Oncologico Regional haematological support. By day 14, there was minimal radiation in Cibao. Santiago Dominican Republic. the whole body image and the child received her bone marrow transplant. In this paper we present experience in Dominican Republic on There was marked improvement in the tumour size after 6 weeks Radiopharmaceutical Therapy. In our country, there are 8 Center of therapy, with improvement in the alkaline phosphatase level with Nuclear Medicine Department. Only, 7 centers are working (from 1350Iu, before treatment to 350 post treatment). This was with Radiopharmaceutical Therapy. Radioiodine treatment with confirmed by serial MDP bone scan. High dose Sm-153 with stem I-131 in Thyroid diseases(Thyroid Cancer and Hypertyroidism). cell transplant is considered view a promising method in the This is only Nuclear Medicine therapy available in Dominican management of osteosarcoma. Republic. The objectives of this paper are to analyze and assess the difficulties and facilities for the development of Radiopharmaceutical Therapy in Dominican Republic. We made surveys with the help of Nuclear Medicine Physicians of different Nuclear Medicine departments. 8 Nuclear Physicians accepted the World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 29. S-23 Abstracts: ICRT-2005 tumors that are thought to arise from cells in the neural crest from 026-EST the pelvis to neck, produce high levels of the urinary Radiosynovectomy: First Results in Estonia catecholamines vanillylmandelic acid (VMA) or homovanillic Nazarenko S, SamarinaG, Poksi A acid (HVA) in more than 90% of cases, and often metastasize to North Estonia Medical Centre, Tallinn, Estonia; Department of bones, bone marrow (BM), lymph nodes, and the liver.I-123 Nuclear Medicine, East Tallinn Central Hospital, Estonia MIBG andI-131 MIBG are clinically important radiopharmaceuticals, which are routinely used for diagnostic In Estonia first radiosynovectomy (RSE) was carried out in 2001 imaging and treatment of NB. 90% percent of NB takes up the at Tallinn Central Hospital, which has remained the only MIBG. If, however, the MIBG cannot successfully attach to a institution in North Estonia performing these procedures. Purpose patient's tumor, it cannot be used to find or treat it. A 20-month-old of this study was to analyze the results and the clinical experience girl presented with a 6-month history of a rapidly growing tumor gained during the period of September 2001 January 2005. We mass 3.5 cm in diameter in the left orbital region. The first CT scan performed RSE in 10 knee joints of 7 patients. Our patient revealed a soft tissue tumor 22 x 28 mm, extending from the population consisted of 3 males and 4 females (mean age 34, range inferolateral wall of the left orbit and destroying the surrounding 16-48). There were 6 patients with rheumatoid arthritis (RA) and bone (os zygomaticus). CT scans of the chest and abdomen were chronic synovitis and 1 patient with haemophilia (HE) who had negative. Histopathology showed high malignancy (G3) of NB one episode of hemarthrosis eight month prior to RSE. In RA the (immunohistochemical reactions: NSE positive, CgA positive, duration of the disease was ranging from 2 month to 20 years. All SY positive, Ki-67 70% of tumor cells positive). First BM RA patients were resistant to anti-inflammatory drugs, histological examination revealed no pathological findings. immunosupressants and intraarticular steroid therapy. Prior to Urinary VMA and HVA levels were within the normal range. Tc- RSE, conventional rheumatologic evaluation and MRI scan were 99m MDP scans showed increased uptake of radiopharmaceutical carried out, revealing the thickness of synovia of 2-5 mm, and in the bones around the left orbital region but no evidence of minimal or no cartilage damage. In our HE patient chronic skeletal metastases. 123I-MIBG studies revealed a hypermetabolic hypertrophic synovitis associated with haemarthrosis did not focus in the left orbital region, concordance with the CT and bone respond to haematological treatment: replacement of the missing scans. The child was treated with preoperative chemotherapy, but clotting factor, intermittent steroids, immobilization, physical without any results: the CT-scan performed four months later therapy. According to MRI, the thickness of synovia was patchy, showed that the tumor had grown to 45 x 37 x 40 mm. The clinical 5-26 mm, the cartilage damage was absent. For RSE, intra- test demonstrated the progress of the disease and the tumor at that articular injection of radiocolloid was carried out in aseptic stage was inoperable. Clinicians decided to change the conditions and under local anesthesia. Treated joints were chemotherapy regimen and a CT study carried out three months immobilized for 2 days. In 5 out of 6 RA patients the injection was later showed that the tumor had decreased to 26 x 10 x 30 mm. The performed once, in one RA patient four times. In order to patient was operated on whereby the tumor was partially resected minimize local inflammation and lymphatic clearance from the left orbital region. A MRT scan performed two months glucocorticoids were administered together with radioisotope later showed progression of tumor mass to the orbit (50 x 40 x 30 agents. In three patients (2 with RA and 1 with HE) 27 mCi of 166- mm) with destruction of the maxillary sinus and metastases to BM Ho-FHMA was injected, and in remaining four patients with RA - in vertebrae and femoral bones. A subsequent BM biopsy 4-6 mCi of 90-Y radiocolloid was used. All joints with Ho-FHMA demonstrated evidence of high malignancy of the tumor were checked for radiocolloid leakage by subsequent gamma metastases. Repeated Tc-99m MDP bone scans were not positive camera imaging. Treatment response was evaluated from 2 to 6 for bone metastases. This year the patient had different month after RSE by presence of tenderness and swelling of treated combinations of chemotherapy constantly, but without any joint, functional status, and using visual analogue pain scale (0-10 clinical success. At that stage a clinician of the Pediatric point gradation). In 6 cases (5 RA and 1 HE) repeated MRI was Oncology Department decided to perform I-131 MIBG therapy. performed after RSE. Improvement in local clinical signs was The child's parents received information about the procedure and noted in 6 RA cases out of 9 (67%), insufficient improvement - in 3 specific instructions concerning radiation safety precautions. In (33%). In two RA patients (5 therapy cases) with follow-up MRI, order to minimize thyroidal uptake of free iodide in the child and decrease of synovia up to 0,5-2 mm was observed. In one RA her father, they were given 200 mg of oral potassium iodide per patient RSE was performed four times, providing relief in clinical day, which was started 48 hours before I-131 MIBG signs after every treatment, and decrease of synovia after the 1st administration and continued up to 10 days after the therapy. The and 2nd injection. In HE we did not observe any change in synovia, administration of the 162 mCi I-131 MIBG was performed during but during the follow-up period of more than 3 years no repeated 2.5 hours with a radiation safety system, the patient being under haemarthrosis has occurred. We did not observe any general or supervision in an isolated and monitored hospital room. Side local symptoms of radiation sickness in our patients. In effects, such as mild nausea and vomiting, were observed conclusion, RSE is a safe and effective tool for the management immediately after the administration. During the therapies the of synovitis in RA and HE patients. child watched TV and videos, drew pictures and played with her games or toys. Radiation dosimetry was performed daily. After the 027-EST I-131 therapy scan (the whole body and SPECT of the head and Our First Experience in the Application of I-131 MIBG in a neck) we verified the presence of multiple sites of the tumor in the Patient with Neuroblastoma (A case report) head (the left and right orbital region and the left parieto-occipital Samarina G, Poksi A region) and bone marrow infiltration in the left arm and both lower Department of Nuclear Medicine, East Tallinn Central Hospital, limbs. The patient went home on the 8th day after the injection of I- Estonia 131 MIBG. During the first two weeks the patient's clinical condition was stable. During the next two weeks the clinical test Neuroblastomas (NB) belong to a group of neuroendocrine showed rapid progression of the tumor in the left orbital region (it World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 30. S-24 Abstracts: ICRT-2005 had grown app. 2-3 times) but also tumor mass development in the radiopharmaceutical in the bone metastases and a 50% uptake in right orbital region. Mild BM depression, such as leucocytopenia the cortical and trabecular bone. For calculation of the uptake and thrombocytopenia, was verified. After a 4-week interval the I- animals studies were developed to induce osteoblastic bone 131 MIBG therapy was repeated at the same dose level. The metastases by intra-ossär administration of prostate cancer cells. second therapy scan revealed that the primary tumor in the head In autoradiographic studies (BAS 500, Fuji; resolution of 0.5 µm) had grown considerably and BM metastases had spread further - bone metastases and skeleton were investigated after 188Re-HEDP. the first therapy had had no effect. In this case I-131 MIBG In the bone metastases a tumour to muscle ratio (T/M) of 48 ± 7 treatment failed to produce the desired result due the rapid and a tumour to non-tumour ratio (T/NT) of 9.7 ± 1.5 (7.5 to 11.7) progression of NB. The patient's clinical condition kept was found. The distribution in the metastases was inhomogeneous deteriorating after the second MIBG therapy and a few months with a minimal T/NT of 7.0 ± 1.0 (4.9 to 8.5) and a maximal T/NT later the patient died. In conclusion, an accurate preoperative of 17.4 ± 2.7 (11.6 to 22.6). The ratio between the trabecular and diagnosis of NB with I-131 MIBG is of crucial importance in cortical bone in non-tumour bone was 68.6 ± 7.2% to 31.4 ± 7.2 %. choosing the appropriate strategy for the management of this kind The inhomogeneous distribution could favour high beta energy of tumor. Our patient had progressive and intensely pretreated radionuclides for a more homogeneous dose distribution in bone stage IV disease. MIBG therapies were only performed after the metastases. The MIRDOSE calculation underestimates the bone other treatment modalities had failed. We do not have any marrow dose; the uptake in the trabecular bone is higher than in the experience with MIBG therapy in earlier stages of NB, but we cortical part. The higher uptake in the trabecular bone decreases believe that this treatment would be more helpful in patients with the hypothetic dose reducing effect of low beta energy slower NB tumor progression. radionuclides to the bone marrow. 028-GER References Therapeutic Efficacy and Dosimetric Aspects of Rhenium- 1. Tu SM, Millikan RE, Mengistu B, et al. Bone-targeted therapy 188-HEDP in Bone Pain Palliation for advanced androgen-independent carcinoma of the Knut Liepe prostate: a randomised phase II trial. Lancet 2001;357:336-41. Department of Nuclear Medicine, University Hospital Dresden, 2. Soerdjbalie-Maikoe V, Pelger RC, Lycklama a Nijeholt GA, et Germany al. Strontium-89 (Metastron) and the bisphosphonate olpadronate reduce the incidence of spinal cord compression Bone metastases are a frequent complication of cancer, occurring in patients with hormone-refractory prostate cancer metastatic in up 70% of patients suffering from advanced breast or prostate to the skeleton. Eur J Nucl Med Mol Imaging 2002; 29:494-8. cancer and often present with severe bone pain. In this purpose the 3. Liepe K, Kropp J, Runge R, Kotzerke J. Therapeutic efficiency radionuclide therapy is a useful option for cancer patients. of rhenium-188-HEDP in human prostate cancer skeletal Different radionuclides are described, such as 89Sr, 32P, 153Sm- metastases. Br J Cancer 2003; 89:625-629. EDTMP, 186Re-HEDP, 131I-BDP3, 90Y, 117mSn-DTPA, 188Re- 4. Liepe K, Franke WG, Kropp J, Koch R, Runge R, Hliscs R. HEDP and 188Re-DMSA. The most experiences are available for [Comparison of rhenium-188, rhenium-186-HEDP and 89 Sr. An indication for the treatment are patients with osteoblastic strontium-89 in palliation of painful bone metastases]. metastases, bone pain, sufficient bone marrow function and at Nuklearmedizin 2000; 39:146-51. least of three bone metastases visualized in bone scan. A 5. Liepe K, Runge R, Kotzerke J. The benefit of bone-seeking bisphosphonate therapy, a chemotherapy with lower bone marrow radiopharmaceuticals in the treatment of metastatic bone pain. toxicity or a local field external beam radiotherapy represent no J Cancer Res Clin Oncol 2005; 131:60-6 contraindications, especially because the reported synergistic 6. 1. Tu SM, Millikan RE, Mengistu B, et al. Bone-targeted effects to the systemic radionuclide therapy (1,2). therapy for advanced androgen-independent carcinoma of the In 33 treated patients (breast and prostate cancer) we investigated prostate: a randomised phase II trial. Lancet 2001;357:336-41. the effect of 188Re-HEDP on pain relief, analgesic intake and 7. 2. Soerdjbalie-Maikoe V, Pelger RC, Lycklama a Nijeholt GA, impairment of bone marrow function. There were an improvement et al. Strontium-89 (Metastron) and the bisphosphonate on the Karnofsky performance scale from 74 7% to 85 9% 12 olpadronate reduce the incidence of spinal cord compression weeks after therapy (p= 0.001). The pain score showed a in patients with hormone-refractory prostate cancer metastatic maximum decrease from 44 ± 18% to 27 ± 20% in the 3rd to the 8th to the skeleton. Eur J Nucl Med Mol Imaging 2002;29:494-8. week after therapy (p = 0.009) and 76% had a pain relief (20% 8. 3. Liepe K, Kropp J, Runge R, Kotzerke J. Therapeutic were pain free). The maximal differences between the values of efficiency of rhenium-188-HEDP in human prostate cancer platelets and leukocytes before and after therapy were not skeletal metastases. Br J Cancer 2003;89:625-629. statistically significant (p= 0.021 and p= 0.094) (3). In 105 9. 4. Liepe K, Franke WG, Kropp J, Koch R, Runge R, Hliscs R. investigated patients treated with different radionuclides (89Sr , [Comparison of rhenium-188, rhenium-186-HEDP and 153 Sm-EDTMP, 186Re-HEDP, 188Re-HEDP and 89Sr in combination strontium-89 in palliation of painful bone metastases]. with chemotherapy) no different therapeutic efficacy of the Nuklearmedizin 2000;39:146-51. treatments were observed (4), (5). In dose calculation of 188Re- 10. 5. Liepe K, Runge R, Kotzerke J. The benefit of bone-seeking HEDP a radiation dose of 3.83 ± 2.01 mGy/MBq (12.6 Gy for radiopharmaceuticals in the treatment of metastatic bone pain. 3300 MBq) for bone metastases and 0.61 ± 0.21 mGy/MBq (2 Gy J Cancer Res Clin Oncol 2005;131:60-6. for 3300 MBq) were found. With the introducing of radionuclide 6. Palmedo H, Manka-Waluch A, Albers P, et al. Repeated treatments with chemotherapy and repeated treatments (1), (6), bone-targeted therapy for hormone-refractory prostate the calculation of bone marrow radiation-absorbed dose is more carcinoma: tandomized phase II trial with the new, high- significant. But the dose calculation by MIRDOSE based on the energy radiopharmaceutical rhenium-188 hydroxyethyliden- hypothesis of a homogeneous distribution of the ediphosphonate. J Clin Oncol 2003;21:2869-75. World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 31. S-25 Abstracts: ICRT-2005 029-GER scintigraphy, F-18-Fluoride-PET/CT, renal scintigraphy (MAG Clinical Results of Intravenous and Intra-Arterial Peptide 3), GFR measurements (DTPA) and monthly laboratory tests Receptor Radionuclide (haematology, liver enzymes, renal parameters, tumour Therapy (PRRT) using Y-90 and Lu-177 DOTA-TYR3- markers). (Figure-1 and 2) OCTREOTATE (Y-90 DOTA-TATE) in 151 patients with Results revealed 2 patients with complete remission (de novo metastatic progressive neuroendocrine tumors (NET) therapy), Partial remission (PR) in 37 %, Stable disease (SD) in Baum RP, Söldner J, Strauß H-J 52 % and disease progression (DP) in 11%. Objective tumour Dept. of Nuclear Medicine / Center for PETCT, Zentralklinik response (including improvement of symptoms) was seen in 85 Bad Berka, Germany % of the patients. A few adverse effects were also noted: Nausea and vomiting occurred in 35 % of female, and in 15 % of male We investigated the anti-tumor efficacy and adverse effects of patients. Anemia, leucocytopenia and thrombocytopenia (G2-3) the somatostatin analog octreotate labelled with Y-90 or Lu-177 observed in less than <15 %. None of the pts developed in patients with progressive neuroendocrine tumors and severe myelodysplastic syndrome. No hair loss was observed. tumour burden. We conclude that PRRT with Y-90/Lu-177 DOTA-TATE results 151 patients (69 f and 82 m, age range=19-81 yrs), 307 in a high response rate with significant improvement of clinical administrations, Mean activity per cycle 3.35 GBq (max. 7000 symptoms; the treatment is tolerated with low toxicity and few MBq) and time between cycles 3 to 6 months. 7 pts received adverse effects and shows promising results also in pts with intra-arterial injections (8 cycles). All patients were selected progressive neuroendocrine tumours after biological treatment based on high SST-R expression as proven by (interferon/sandostatin) or after chemotherapy. Renal toxicity immunohistochemistry and Ga-68 DOTA-NOC receptor can be reduced by prolonging the intervals between therapy PET/CT or somatostatin scintigraphy. Restaging was done using cycles and reducing the maximum activity per cycle (“Bad Ga-68 DOTA-NOC PET/CT, MRI, FDG-PET/CT, SST-R Berka concept”). Figure-1. Intra-arterial Peptide Receptor Radiotherapy using Y-90 DOTA-TATE World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 32. S-26 Abstracts: ICRT-2005 Figure-2. Intravenous and Intra-arterial Peptide Receptor Radionuclide Therapy (PRRT) 030-GER pulmonary embolism (immobilization of the knee), lymphoedema Radiosynovectomy in the Treatment of Arthritis or loss of motion. In the treatment of the knee a prophylaxis with Knut Liepe heparin is necessary to protect the patients for a pulmonary Department of Nuclear Medicine, University Hospital Dresden, embolism. Germany The clinical outcome is depending from the primary disease and the stage of arthrosis. Kresnik at al (1) reported in 2190 treated Radiosynovectomy is a useful therapeutic option that involves joints an overall response rate of 73 ± 17%. A higher response rate radiopharmaceutical injections into joints, especially to treat was observed in patients with early stage of arthrosis (73 ± 12%) to rheumatoid arthritis. The indications included different kinds of patients with advance stage (52 ± 24%). The best results had arthritis, such as rheumatoid arthritis, psoriatic arthritis, patients with hemophiliac arthritis (91 ± 4%). In our hospital were Bechterew's disease, hemophiliac arthritis, osteoarthritis, but also treated up to 10.000 joints with a mean response rate of 70-80%. patients with joint prosthesis and synovial effusion. There are There was a higher response rate in larger joints with 81 ± 5% three commercial available radiopharmaceuticals for the (knee, ankle joint, shoulder and wrist) in comparison to the smaller treatment: yttrium-90 for the knee (185 to 250 MBq), rhenium- joints with 74 ± 4% (MCP, PIP, DIP, thumb base, MTP). 186 for larger joints (shoulder and hip with 111 MBq; elbow, wrist, Unfortunately, 67% of the treated joints are small joints, ankle joint with 74 MBq) and erbium-169 for smaller joints especially in patients with rheumatoid arthritis. The duration of (acromioclavicular joint with 37 MBq, thumb base and MTP I response ranged from 3 months to > 6 years. In patients with with 30 MBq, MCP and MTP II-V with 22 MBq, PIP with 18.5 rheumatoid arthritis the duration of response is depends from the MBq, and DIP with 15 MBq, respectively). Decisive for the activity and the stage of the disease and these patients need an treatment is a positive sign for arthritis in the two-phase bone scan effective disease modifying treatment. Also patients with advance with 99mTc-HMDP (high uptake in the blood pool phase). Only stage (Larsen 4) showed partial good results, especially patients for radiosynovecotmy in the knee an ultrasound with an evidence with haemophiliac arthritis. of effusion is sufficient. Side effects by the treatment are rare, such In large centres the radiation protection for the medical staff is as temporary radiation or crystal synovitis, tissue necrosis (extra- important. We observed a high beta dose of 22.1 µSv/MBq for the articular fraction or intra-articular), joint infection (1 of 35,000 forefinger using only a syringe protection in treatments of knees ( joints) or effects due to the immobilisation (thrombosis, 90 Y), this resulted in a annual radiation dose > 1000mSv for 250 World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 33. S-27 Abstracts: ICRT-2005 treated knees (normal for large centres). The high finger exposure for DOTA-TATE. in treatment of the knee (Y-90) could be reduced by around 95% For whole-body, the first effective half-time (t1/2 alpha) was longer using a simple manipulator (holding-forceps) for the fixation of for DOTA-NOC (NOC 2.8+/-1.2h; TATE 2.0+/-0.6h), as well as the needle during the administration of the 90Y (2). The the second elimination half-life (t1/2 beta) (NOC 58.0+/-11.0h; radiosynovectomy is safe if it performed by trained staff. We TATE 53.9+/-13.6h). In normal tissue, the first half-time was observed only one patient with joint infection in the time of longer for DOTA-NOC (NOC 3.0+/-0.8h; TATE 2.6+/-1.1h), introducing the procedure and no case with radionecrosis. however t1/2 beta was longer for DOTA-TATE (NOC 42.9+/-3.8h; Summary: Radiosynovectomy is an effective and fast procedure TATE 46.1+/-13.9h). The t1/2 alpha and beta were longer for in the treatment of arthritis with a low rate of side effects. DOTA-TATE in the kidney (NOC 0.9+/-0.7h and 69.4+/-14.2h; TATE 1.6+/-1.4h and 74.9+/-34.8h, respectively). For the spleen, References only t1/2 beta was calculated which was longer for DOTA-NOC 1. Kresnik E, Mikosch P, Gallowitsch HJ, et al. Clinical outcome (NOC 74.5+/-3.2h; TATE 73.0+/-10.6h). In metastases, the of radiosynoviorthesis: a meta-analysis including 2190 treated second half-time was slightly shorter for DOTA-TATE (NOC joints. Nucl Med Commun 2002; 23:683-8. 78.0+/-7.6h; TATE 75.0+/-25.0h). 2. Liepe K, Andreeff M, Mielcarek J, et al. [Beta-radiation The resulting whole-body dose was lower for DOTA-TATE (0.20 exposure at the finger tips during the radionuclide Sv) as compared to DOTA-NOC (0.50 Sv). There were no synovectomy]. Nuklearmedizin 2003;42:104-8 significant differences between both peptides concerning the mean absorbed kidney dose (3.0 Gy) and the absorbed dose in the 031-GER spleen (5.0 Gy). The mean absorbed tumor dose was 58+/-59 Gy Peptide Receptor Radionuclide Therapy (PRRT) of for DOTA-TATE and 28+/-18 Gy for DOTA-NOC. Neuroendocrine Tumors: First Comparative Results using the The kinetics in blood showed a great variation (Table 1). Somatostatin Analogues Lu-177 DOTA-NOC and Lu-177 These first results demonstrate that the higher in vitro affinity of DOTA-TATE DOTA-NOC leads to a higher uptake in normal tissues and Wehrmann C, Senftleben S, Baum RP therefore increases the whole-body dose. However, Lu-177 Department of Nuclear Medicine / Center for PET-CT, DOTA-TATE was superior to Lu-177 DOTA-NOC concerning the Zentralklinik Bad Berka, Germany tumor dose due to the higher initial tumor uptake (esp. after 24 hours) and a very similar t1/2 beta in the metastases. Peptide receptor radionuclide therapy (PRRT) is used in our department since 5 years (approx. 400 applications) for the These preliminary results have to be verified in future studies in a treatment of patients with metastatic neuroendocrine tumors. Of larger number of patients. all known peptides, the somatostatin analogue DOTA-NOC Half-time 1 Half-time 2 Half-time 3 Residence Time Red Marrow Dose in h in h in h in h in Sv shows in vitro the highest affinity to somatostatin receptors (sstr) 3 Mean 0.25 1.78 17.96 0.13 0.18 and 5 and a very high affinity to sstr 2. We studied the in vivo STD 0.22 0.77 10.81 0.04 0.09 behaviour of the two peptides DOTA-NOC and DOTA-TATE Min 0.07 1.05 6.19 0.09 0.10 (highest affinity to sstr 2) by the use of different parameters like Max 0.77 3.29 35.73 0.20 0.40 tumor and organ uptake, effective half-lifes (kinetics) and mean absorbed organ and tumor doses. 032-GER We studied 27 patients with metastatic neuroendocrine tumors Intacoronary Radiation Therapy: Placebo Controlled Study: with high somatostatin expression, as verified prior to treatment A Report by Ga-68 DOTA-NOC receptor PET/CT or somatostatin receptor Kropp J1, Reynen K2, Koeckeritz U2, Knapp FF3 scintigraphy (Tc-99m EDDA-Hynic TOC or In-111 OctreoScan, 1 Deptt. of Nuclear Medicine, CTK Hospital, Cottbus, Germany; planar and SPECT). 2 Deptt. of Cardiology, University Hospital Dresden, Germany; 22 patients (8M and 14F; aged 619 years) were treated with 2500 3 Nuclear Medicine Program, ORNL, Oak Ridge, USA 6790 MBq Lu-177 DOTA-TATE. Another 5 patients (1M and 4F, aged 6310 years) were treated with 4000 7400 MBq Lu-177 Intracoronary radiotherapy (IRT) with ß- and ?-emitters has been DOTA-NOC. Labelling efficiency and radiochemical purity using shown to reduce the rate of restenosis after percutaneous coronary Lutetium-177 chloride (obtained from PerkinElmer Life interventions (PCI) and to have a beneficial effect on the clinical Sciences, USA) were constantly over 99.5 %. Whole-body scans outcome of these patients (2). This presentation addresses the (anterior/posterior) were performed at 0.5h, 3h, 24h, 48h, 72h and question whether IRT applied by open radionucli- des is also able 96h p.i. ROIs were drawn over the whole-body, organs, and to achieve this aim: the Dresden prospective, RAndomized, different metastases (mainly in the liver). Blood samples were placebo-controlled, double-blind, IN-stent restenosis trial obtained in 12 patients after therapy with Lu-177 DOTA-TATE (DRAIN) using the easy to handle, self-centering Rhenium-188 over 5 days for calculating the kinetics in blood. perrhenate liquid-filled standard PTCA balloon. In DRAIN 210 The ROI results were used to determine the uptake and effective symptomatic patients (pts) for CAD with a mean age of 62 years half-life in different organs (kidney, spleen, liver, bone etc.) and (253 m, 166 fm) with in-stent restenosis underwent therapy (IRT) the tumor residence times. By means of geometric mean, and after or sham procedure (SHP) with 45 pts in an initial pilot study. 165 background correction, the ROI results were also used to calculate pts were included then in the randomized part of the study from the estimated absorbed organ and tumor doses using the OLINDA which 156 (95%) had 6-month quantitative angiographic follow- software. up. One-year follow-up was obtained from 164 pts. After routine Compared to Lu-177 DOTA-TATE (=100%), the uptake of Lu- re-PTCA a second standard balloon was placed into the PTCA area 177 DOTA-NOC was higher for the whole-body (45%) and for 5mm longer at each end than first balloon (5) and filled with ß- normal tissues (28%), and also in the spleen (11%) and in the emitting liquid Re-188 at 3 atm. Geographical miss was carefully kidneys (5%). In contrary, the uptake in the tumor was 13% higher avoided. Irradiation time was 400 +/- 122 sec (range 240 to 890 World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 34. S-28 Abstracts: ICRT-2005 sec) to achieve a dose of 30 Gy at 0.5 mm depth of the vessel wall which seem to suppress the growth of smooth muscle and endothelial cells which are considered to be mainly responsible for restenosis (3). All patients had long-term strong antiplatelet therapy after IRT of at least 1 year (4). Figure 2B. 6 months after PTCA and IRT Figure 1 Clinical situation in the catheter laboratory during IRT. ISAT: (p=0.03). The late lumen loss was 0.25+/-0.38 in IRG and 0.39+/- Isotope (188Rhenium) storage and transfer unit 0.40 (p<0.05). At 1-year clinical follow-up overall event-free survival (death, MI, TVR) was 87 % in IRT and 74% in SHP (p < All procedures were performed without any problem (Figure 1) 0.05). All other parameters were not significantly different in both In the pilot study consisting of 45 pts (group I: 25 pts only IRT, groups, but diabetes was even more frequent in IRT (44% vs. group II: 20 pts IRT+new stent) the restenosis rate in the second 27%). group was 63 % compared to the expected rate of 60% whereas in In conclusion, intracoronary radiation therapy with ß-emitting the first group the rate was 20 % (p < 0.03) which is in agreement rhenium-188 liquid-filled balloon is an easy to perform, with other studies (1). Therefore in DRAIN IRT + new stent was inexpensive, safe and effective option to prevent re-restenosis in avoided in the following randomized study (Figure 2). In our cases of (re)stenosis. But only patients with in-stent restenosis randomized study two episodes of stent thrombosis with seem to benefit clinically from the procedure during long-term subsequent MI occurred in follow-up (after 6 days in SHP; after 8 follow-up if TLR, TVR and MACE are considered as endpoints. months in IRT). Overall restenosis rate was 35%, 19/78 (24%) in IRT and 31/78 (40%)in SHP (p=0.04) (Figure 2). References 1. Cheneau E, Wu Z, Leborgne L, Ajani AE, Weissman N, Pichard AD, Satler LF, Kent KM, Mintz G, Waksman R. Additional stenting promotes intimal proliferation and compromises the results of intravascular radiation therapy: an intravascular ultrasound study.Am Heart J 2003; 146(1): 142- 145 2. Grise MA, Massullo V, Jani S, Popma JJ, Russo RJ, Schatz RA, Guarneri EM, Steuterman S, Cloutier DA, Leon MB, Tripuraneni P, Teirstein PS. Five-year clinical follow-up after intracoronary radiation. Circulation 2002; 105: 2737-2740 3. Henning E, Dittmann H, Wiskirchen J, Bantleon R, Kehlbach R, Claussen CD, Duda SH. Dose dependent effects of the combined beta-gamma-emitter 188Rhenium on the growth of human vessel wall cells. Fortschr Roentgenstr 2004; 176:404- 408 4. Krötz F, Schiele TM, Zahler S, König A, Rieber J. Kantlehner R, Pöllinger B, Dühmke E, Theisen K, Sohn HY, Klauss V. Sustained platelet activation following intracoronary beta irradiation. Am J Cardiol 2002; 90:1381-1384 5. Syeda B, Siostrzonek P, Schmid R, Wexberg P, Kirisits C, Denk S, Beran G, Khorsand A, Lang I, Pokrajac B, Potter R, Glogar D. Geographical miss during intracoronary Figure 2A. Before PCI of in-stent restenosis and IRT irradiation: impact on restenosis and determination of There was no preferred location of the restenosis. Mean diameter required safety margin length. J Aam Coll Cardiol 2002; stenosis amounted to 42 +/-19% in IRT and 51+/-22% in SHP 40:1225-1231 World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 35. S-29 Abstracts: ICRT-2005 033-GER our scientific team to label a novel Bombesin (BN)-like peptide Radionuclide Therapy of B-NHL with Y-90 Epratuzumab: A with Re-186. The new derivative under study is: Gly-Gly-Cys- Report of the Multi-Centre trial Aca-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met- Kropp J5, Chatal JF1, Harousseau JL2, Griesinger F3, Meller J3, CONH2, where Aca: 6-amino-hexanoic acid (BN1.1). Rhenium- Freundschuh MP4, Kirsch CM4, Naumann R5, Huglo D6, 186 is an attractive radioisotope for targeted radionuclidic therapy Morschhauser F6, Lateiner J7, Wegener WA7, Horak ID7 and because of its short half life (T1/2 =89.4h), its ß-particle emission Goldenberg DM7; (Eß = 1.07MeV, Eß = 0.93MeV) and its ?-emission (E? = 1 Institut de Biologie, INSERM, Research Unit 4, Nantes, France; 122KeV, E? = 137KeV, E? = 630KeV and E? = 768KeV) suitable 2 Service d'Hematologie, Centre Hospitalier Universitaire, Nantes, for simultaneous external measuring. In the present work we have France; 3Georg August University, Göttingen, Germany; developed and studied the methodology for the labeling of BN 1.1 4 Saarland University Medical School, Homburg/Saar, Germany; with 186Re of high specific activity. We have studied the labeling 5 conditions in relation, to the production date of 186Re and to the University Hospital Dresden, Dresden, Germany; 6Centre pH of the Rhenium solution. We have also studied the labeling Hospitalier Régional Universitaire de Lille, Lille, France and 7 yield in relation to the pH, the concentration of the reducing agents Immunomedics, Inc, Morris Plains, NJ, United States. and the quantity of the peptide derivative. The radiolabeling yield was checked by High Performance Liquid Chromatography The advantages of increased efficacy of RAIT compared to the (HPLC), and by Instant Thin Layer Chromatography (ITLC-SG). naked antibody are at expense of temporary reversible bone The obtained labeling yield was more than 95% with high marrow suppression. An ongoing, phase I/II, multi-center, dose- radiochemical purity. The stability of the product was studied at escalation trial in patients with relapse of a B-NHL is assessing different time intervals and storage conditions. The radiolabeled safety and efficacy of Y-90-epratuzumab administered weekly for product is stable for at least 96 hours post labeling. Preliminary 2 or 3 consecutive weeks to achieve relatively high fractionated Y- biodistribution experiments in normal and pathological models 90 doses (> 5 mCi/kg BW). Patients with indolent and aggressive are in progress. We conclude that Rhenium186 is an attractive NHL who failed prior therapy were eligible for this study. Thirty- radioisotope for therapeutic use in radiopharmaceuticals, due to seven patients have been revealed into two dose groups without its nuclear characteristics. The bombesin analog BN1.1 has achieving MTD (total 90Y dose, 30 mCi/m2). There were 18 already shown a fine targeting behavior in biological models when follicular, 10 mantle cell, and DLBC-NHL. In 16 cases there was a labeled with 99mTc. For all the above reasons we chose to label foregoing BMT. The therapy consisted of 2-3 weekly injections of and study the peptide derivative BN1.1 with Re-186. The Y-90-hLL2 in dose steps of 3x5 3x10 mCi/ m2 (high-dose group radiolabeling process has yielded a stable and promising without BMT) or 2x2.5 mCi/m2 (low-dose group with prior BMT). radiolabeled biomolecule which can be used for targeted In the frame of the first infusion there was added In-111-hLL2 to radiotherapy. check the targeting of the tumour by imaging at day 3-5 post injection. In the low-dose group in 2 cases there were hematologic 035-GRE DLT noticed so that in this group MTD was achieved. In the high- Patient-specific Dosimetry of I-123-mibg in Diagnosis dose group at 3x 10 mCi/ m2 there was only one DLT obvious. For Improvement Of Dose Estimation in I-131-Mibg Adrenal Except these non-lethal cytopenias no significant toxcicity was Tumours Therapy noticed. Also a HAMA induction was not substantiated. Five Lyra M, Phinou P, Papanikolos G, Jordanou J, Limouris G, patinets without additional toxcicity were treated a second time Vlahos L Of the 37 patients, 23 (62%) had an objective response (OR) by Department of Radiology, University of Athens, Athens, Hellas, IWG criteria, including patients with indolent and aggressive Greece disease [12/17 (70%) and 11/20 (55%), respectively], across histologies [follicular NHL, 13/18 (72%); DLBCL, 7/9 (78%); In this paper we present a patient-specific dosimetric approach mantle cell, 4/10 (40%)], and in patients failing rituximab (10/16, using scintigraphic data from children undergoing diagnostic 63%). Most ORs were complete responses (CR/CRu, 15/23), and examinations with I-123-MIBG in order to estimate the adsorbed with follow-up now available in 15 CR/Cru responders, all had dose in a therapeutic treatment with I-131-MIBG and to responses > 23 mo, including 2 patients continuing > 2.5 yrs. Dose administer the optimum dosage to each patient specifically. I-123- escalation continues after 5/6 patients (83%) in the last cohort MIBG and I-131-MIBG scintigraphy has been established as a receiving 10 mCi/ m2 x 3 weekly infusions had an objective primary method for localization of lesions in patients with response, including 4 patients with CR/CRu. In conclusion, this neuroblastoma. Dosimetric considerations (long physical half- fractionated schedule of 90Y-labeled humanized anti-CD22 time of 8.04 d and beta emission) limit the amount of I-131-MIBG antibody appears safe and efficacious in patients with recurrent administered for diagnostic purposes. Moreover, the gamma NHL. Dose escalation continues after achieving 65% complete camera efficiency of detection of the 364 keV photon of I-131 is responses at a 30 mCi/m2 cumulative 90Y-dose. significantly low. This makes I-123-MIBG (with a short half-time of 13.2 h and a useful gamma energy of 159 keV), the diagnostic 034-GRE adrenomedullary scintigraphic agent of choice, with a sensitivity Labeling of a Bombesin Analog with Rhenium-186 of 88.5% and a specificity of 98.5%. Adult biokinetic data used for Koumarianou E, Bouziotis P, Zikos C, Mitsokapas N, absorbed dose estimates in children, introduce another inaccuracy Xanthopoulos S, Varvarigou AD, Archimandritis SC parameter for dosimetry. N.C.S.R."Demokritos", Neapoleos & Grigoriou E, 15310 Aghia In a series of 16 children, examined diagnostically by I-123- Paraskevi Attikis, P.O.Box 60228, Hellas, Greece MIBG for neuroblastoma, the calculation of tumour doses was achieved by accurate quantification of planar scintigraphy, The need for the development of a new generation of repeated twice for each patient, before therapy decision was made. radiopharmaceuticals with mainly therapeutic applications has led The biodistribution of the compound was also studied in the World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 36. S-30 Abstracts: ICRT-2005 children with neuroblastoma undergoing a diagnostic 036-GRE administration of I-123-MIBG. Comparative Study of Skeletal Dosimetry Methods in Our methodology was to administer to the patient a diagnostic Therapeutic Schemes with Re186 HEDP and Sm153 EDTMP dose of I-123-MIBG of known activity and measured in counts by Papanikolos G, Lyra M, Kontogeorgakos D, Jordanou J, Vlahos g-camera under a standard geometry- , for scanning imaging. L, Limouris G Thyroid uptake of liberated radioiodine was also restricted by Nuclear Medicine Division, Radiology Department, Aretaieion blocking it with stable iodide. Using scans we recorded the Hospital, Athens, GREECE individual patient's biokinetics und uptake of the radiopharmaceutical, calculate tumour and critical tissues' dose Optimum therapeutic management of patients suffering from and extrapolate the results to therapeutic administered activities of metastatic bone pain, requires accurate calculations concerning I-131-MIBG that was predicted to deliver a predefined whole- absorbed dose by metastatic lesions and other critical organs, such body dose. Phantom measurements of scatter and attenuation for as red marrow. Mean absorbed dose, which is the current both I-123 and I-131 radiopharmaceuticals were completed to get parameter used to predict the efficacy of the treatment, can either an energy correction factor. overestimate or underestimate, actual doses delivered in these Total body scintigrams of I-123-MIBG were taken; regions of organs/tissues of interest (TOIs). This study presents differences interest in the scans were determined to measure counts, counts in dosimetric calculations derived utilizing parameters from per pixel and areas. Difference of attenuation between the two different sources (MIRDOSE3, MIRD Pamphlet No 11 and S isotopes (I123 and I-131) was corrected. Using the MIRD values published by Bouchet et al.), in therapeutic schemes with formalism, a single exponential fit drawn through the data from Re186HEDP and Sm153EDTMP. the I-123-MIBG scans was realised. The increased adrenal uptake A set of planar scintigraphic images for 2 groups of patients (1 for in pathological cases results in increase of absorbed dose in Re 186 patients and the other for Sm153 patients) were obtained adrenals and other target organs affected by them. in the following sequence: 2 during the first 24h post injection (the Both I-123 and I-131-MIBG are normally taken up by liver, last of which at 24h post injection) and 2 more from 24h 7d post spleen, myocardium and salivary glands. The normal adrenal injection. Processing of the obtained images utilizing ROI glands are usually not seen, however a faint uptake may be visible quantitative methods, previously calibrated with waterphantom 48-72 h after injection in up to 16% of cases. The hepatic uptake is measurements, determine residence times and radionuclide maximal at 24 h and reduced in very low levels by 72 h. uptakes not only by TOIs but by specific skeletal sites as well. The results indicate substantial inter-patient variation in hepatic Dosimetric calculations were performed using MIRDOSE3 dose delivery, a fact that renders this organ critical in patients computer code, S values from MIRD Pamphlet No 11 and site undergoing radiotherapy with I-131-MIBG. A patient-specific specific Re 186 and Sm 153 S values for several source target dosimetric approach using scintigraphic data from children combinations within trabecular and cortical bone, reported by undergoing diagnostic examinations with I-123-MIBG was Bouchet et al. (J Nucl Med 2000; 41:189 212), along with completed. Assuming that the liver uptake remains approximately cumulative site specific activities derived from values obtained the same in the diagnostic image of a pathological subject, while by image processing. Skeletal averaged Re 186 and Sm 153 S the adrenals uptake is much increased, the ratio of liver to adrenals values were also used from the aforementioned study by Bouchet activity concentration measured in the ROIs of planar scintigrams, et al. can give the altered adrenal uptake for each pathological subject. Time activity curves for various skeletal sites were generated for Using established MIRD data, but correcting for the increased both groups of patients. Absorbed dose distributions along with adrenals uptake, the total absorbed dose to adrenals and other time dose rate curves were derived for both red marrow and organs and tissues was calculated. different regions of the skeleton. Comparisons are made between In our series of 16 children, the median tumour dose was 3.2 these parameters and mean absorbed doses calculated using mGy/MBq, however the variation in dose was great with values skeletal averaged S values, S values from MIRD Pamphlet No 11 reaching up to 20 mGy/MBq in some patients. Whole body and MIRDOSE3 computer code. median dose was found to be 0.12 mGy/MBq and therapeutic ratio It was concluded that mean absorbed dose calculations, in several varied between 120 to below 40 in our patients. The adrenals cases, result in overestimations and underestimations concerning absorbed dose in pathological cases was increased from 8 to 25 actual doses in TOIs. Knowledge of dose distribution and time times. dose rate curves in TOIs are crucial parameters for the assessment In conclusion, our aim was to determine the accuracy of using data the relative biological effectiveness of either an ongoing treatment from I-123-MIBG scans to calculate whole-body dose of the or a treatment about to start. They can also predict the possibility ensuing I-131-MIBG therapy. The use of I-123-MIBG in of dose escalation through multiple administrations of the two diagnosis and I-131-MIBG in therapy of tumours, originating radiopharmaceuticals. from the neural crest, shows high sensitivity and specificity and good therapeutic efficacy with minor toxic side-effects to critical 037-IND tissues. A dosimetry technique has been developed, employing Radiation Synovectomy Versus Intra-articular Steroid quantification of gamma camera scintigrams that allow the Treatment in Inflammatory Arthritis. estimation of tumour uptake and dose before and after therapy Solav S. procedure. However, the wide deviation of dosimetric results SPECT Lab, Nuclear Medicine Services, Opposite Mangeshkar between the various patients, coupled with the fact that the Hospital, Pune, India patients involved were children (radiation-sensitive population), emphasize the need for patient-specific dosimetry methods to be Two groups of patients were treated with intra-articular radio- performed, recording dose burden and optimizing therapy isotope (Group-I) and steroids (Group-II) between Nov 2003 and outcome. December 2004. There were 25 patients (21 males, 4 females; Age range = 12-77 years) in Group-I and 28 joints were treated. All the World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 37. S-31 Abstracts: ICRT-2005 joints had evidence of synovitis on soft tissue scintigram. than three months projected survival. The documented primary Infection and mechanical instability were excluded in all the tumours included cancers of the prostate (n=31), breast (n=46), cases. Out of 28 joints included in the study, 26 joints were treated lung (n=3) and others (one each of ovary, germ cell tumour of with Yttrium-90 colloid and 2 with Rhenium-186 sulfide. The testis, oesophagus, primitive neuroectodermal tumour, Wilm's longest duration of follow up was one year in six joints and the and multiple myeloma). Patients were administered the dose on an shortest duration of follow up was three months in two joints. outpatient basis. 1 mCi/kg body weight of Sm-153 EDTMP None of the patients in Group-I developed any complication such (obtained from Bhabha Atomic Research Centre, a division of the as infection, bleeding or local skin burn. Department of Atomic Energy, Government of India; There were 20 patients (14 males and 6 females; Age range = 32- radiochemical purity >98 %) was given by slow intravenous 76 years) in Group-II. All patients were proven cases of injection, followed by a whole body scan after 2 hours. All patients Rheumatoid arthritis and had evidence of local synovitis on soft were followed up for 16 weeks post-therapy. For primary data tissue scintigrams. analysis the end points of the study were the VAS results and Pre and post treatment scorings were done by the consultant who analgesic consumption. The VAS pain score, analgesic score, was not involved in the treatment of the joints. Scoring was done mobility index and Karnofsky performance scores were recorded using a visual analogue scoring system using a scale of 1-10, with at 4, 8, 12 and 16 weeks, taking the mean of weekly scores, “0” being no relief, “5” being 50% relief and “10” being complete patients were closely followed for onset of pain relief and duration relief. The results are summarized in the following table: of response. If the pain intensity on the VAS decreased for at least two steps for two weeks, while the analgesic score remained at No of joints RS Steroid Chi- Significance least constant; therapy with Sm-153 was considered as efficacious with >/= Group Group square and the patient was a responder. If the pain score or analgesic score 50% pain (N=28) (N=20) (X^2) increased during the follow up period, the patient was considered a relief non responder. Toxicity was evaluated by measuring changes in At 1 month 9/28 16/20 8.87 P<0.01 platelets, leucocytes and haemoglobin during the first 12 weeks of follow-up and was classified by the 5-point toxicity score (32%) (80%) (significant) according to World Health Organization criteria. At 3 13/28 0/20 10.5 P<0.01 Overall response rate was 73 %; the responders showed an months (46%) (0%) (significant) improvement in general condition and a better quality of life. At 6 19/26 1/20 18.6 P<0.001 Therapeutic effect started 4 to 14 days after administration with an months (73%) (5%) (Highly average of 8.8±5.3 days. The effect lasted for 2-8 months; mean duration of response was 3.16±1.88 months. Approximately 12 % significant) of patients were completely pain-free for a period of time. A total In the radiosynovectomy group, it was observed that there was of 46 patients (44 females and two males, age range 32 to 80 years) escalating improvement in the relief from 32% at one month to with Ca breast and painful bone metastases were included for 73% at six months. The second group revealed prompt relief of therapy. Six patients had complete response to therapy (complete symptoms in the early period, i.e. at 4 weeks and there was absence of pain) and were not on any analgesic at the end of the resurgence of symptoms in majority of the joints at six months. four month evaluation period. Subsequently two of these patients received a second dose and three patients received three doses of 038-IND Sm-153. 31 patients had partial response to therapy with a Sm-153 EDTMP Therapy for Bone Pain Palliation in Skeletal decrease in pain score and a decrease in the dose of analgesic Metastases: AIIMS Experience. medication required. Statistically significant reduction in pain Tripathi M, Chandrashekar N, Kumar R, Julka PK, Bal CS and scores and analgesic scores from baseline were seen at 4, 8, 12 and Malhotra A 16 weeks post-therapy. The Karnofsky scale improved in all Department of Nuclear Medicine, AIIMS, New Delhi, India responders. Generally improved mobility accompanied an improvement in pain scores. Nine patients did not respond to Systemic therapy with radionuclides may be the choice of therapy with an increase in pain scores and analgesic index. 31 treatment for palliation of metastatic bone pain owing to its patients with hormone refractory Ca prostate, age 63±8.3 years efficacy, low cost and low toxicity. Imported radionuclides for (range 50 to 80 years) were administered Sm-153 therapy. Four pain palliation, like Sr-89 are expensive; particularly for patients had complete response to therapy and were not on any developing countries. In the Indian scenario, Sm-153 is produced analgesics at the end of the four month evaluation period. in our own reactors as a result of which it is readily available and Subsequently two of these patients received a second dose and two economical. The objective of this study was to determine the patients received three doses of Sm-153. 21 patients had partial efficacy of Sm-153 therapy for bone pain palliation in Indian response to therapy with a decrease in pain score and a decrease in patients with multiple skeletal metastases refractory to other the dose of analgesic medication. Statistically significant modes of therapy. From April 2001 to September 2004, 110 reduction in pain scores and analgesic scores from the baseline patients were enrolled in the study, of whom 86 patients completed data were seen at 4, 8, 12 and 16 weeks post-therapy. The the 16-week follow-up. Inclusion criteria for the patients were: Karnofsky scale and mobility scores improved in all responders. two or more sites of painful bone metastases corresponding to Six patients did not respond to therapy. The response rate in Ca positive sites on bone scintigraphy, progressive pain requiring breast and Ca prostate patients was 80.4 % and 80.6 % increasing level of analgesics, Karnofsky performance score of = respectively. Two Ca lung patients and one case each of ovarian 60, recurrent pain in a radiotherapy field, normal renal function, carcinoma, germ cell tumor testis, cancer oesophagus, primitive normal liver function, platelet count greater than 100,000/cu. mm, neuroectodermal tumor, Wilms tumor and multiple myeloma did leukocyte count greater than 4000/cu.mm. Patients were excluded not respond to therapy. from the study if they had extensive soft tissue metastases and less Haemoglobin, platelets and WBC decreaed by approximately 13 World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 38. S-32 Abstracts: ICRT-2005 %, 23 % and 26 % respectively from baseline values with nadir at studies showed that the DMSA inside the microspheres are present 3-4 weeks and recovery by 6-8 weeks. Grade 3 and 4 in either amorphous crystalline state or in sold solution state. The haematological toxicity was not seen in any patient. Only one IR of released material from microspheres was similar to the IR of patient experienced a flare response, though this was not of 99mTc(V)DMSA. This demonstrated that the chemical nature of associated with a clinical response to therapy. The results of the drug is intact inside the microspheres. If PEG was added in the study showed that Sm-153 EDTMP offers a safe and effective initial stage of preparation with PLGA, the initial burst was very treatment option in Indian patients with painful bone metastases. It high but if the microspheres were coated with PEG after is a well-tolerated single-session procedure that usually achieves preparation, initial burst was drastically reduced. It was found that good pain palliation and sometimes pain-free periods lasting there was significant reduction in overall survival of glioma cells several months. at different point of time. There was a decreasing fraction of viable cells with increased absorbed dose. Thus irradiation by 188Re(V) 039-IND DMSA microspheres caused cell death (actually a regression of Re-188 (v) DMSA -PLGA Microspheres for Targeted Therapy cell division) and resulted the inability of glioma cells to divide. of Neurogenic Tumors Biodistribution studies demonstrated that PEG coated Shukla J1, Kumar R1, Malhotra A1, Maulik SK1, Varma IK2, microspheres did not concentrated in liver. Normally, a foreign Bandopadhyaya Gp1 particle upon injection is coated by blood components Department of Nuclear Medicine, All India Institute of Medical (opsonisation) and rendered 'visible' to the defence system of the Sciences, Ansari Nagar, New Delhi- 110029 INDIA, Center for body, the reticulo-endothelial system(RES). The kpuffer cells of Polymer Science and Engineering Indian Institute of Technology, the liver are extremely efficient at removing particles recognized Hauz Khas, New Delhi-110016, INDIA as foreign. As a consequence, an injected microspheres were directed to a particular cellular sub-set in the liver through the Tumor therapy is constrained by demand to limit damage to process of passive targeting. PEG prevented opsonisation of normal tissue while arresting or at least slowing the growth and microspheres. Microspheres more than 9µm in size were spread of tumor. Chemotherapy and radiotherapy from external accumulated in lungs. sources are restricted by the harm they may impose on essential We conclude that 188Re(V)DMSA is a therapeutic analogous of body function. Dimercapto-succinic acid, a dithiol (containing diagnostic radiopharmaceutical 99mTc(V)DMSA. Accumulation two sulfhydryl, or -SH, groups), is an analogue of dimercaprol and and retention release were size dependent, however variation in used for metal chelation. 99mTc(V) DMSA localize in neurogenic drug release kinetics was observed after coating of microspheres and neuroendocrine tumors. Microsphere based carrier system differentially. For the treatment of tumors, we could tailor the localize radiation dose to tumor sites and may eliminate the toxic microspheres of different size and surface properties. A large side effects that are accompanied with systemic administration of number of cells were killed with radiation emitted by 188 radiation dose. The present study focuses on the characterization Re(V)DMSA microspheres. The b emitting 188Re(V)DMSA and in-vitro and in-vivo ability of 188Re(V)DMSA microspheres as microspheres may be a logical choice for the treatment of therapeutic modality for some tumors. A Tungsten (W-188-Re neurogenic tumors of different organs. 188) generator obtained from ORNL (Oak Ridge National Laboratory, Tennessee, USA) allows us on-site production of a 040-IND beta emitting therapeutic isotope (Re-188) for up to 6 months from Our Experience with the Treatment of 155 Cases of a single generator. Use of DMSA is also cost effective. Carcinoma of Thyroid A solvent evaporation technique was used to encapsulate labeled Anand YNI1, Rajini TR2, Sankar R2. Muthu GS3 and unlabeled DMSA in poly (lactic-co-glycolic) acid (PLGA) 1 “The Nucleus”, Mysore, India; 2Meenakshi Mission Hospital & microspheres. Microspheres of different sizes were prepared. The Research Centre, Madurai, India; 3Tata Main Hospital, size was demonstrated by scanning and transmission electron Jamshedpur, India microscope. Drug loading was studied by differential scanning calorimerty (DSC) and thermogravimetry analysis (TGA) and by Carcinoma Thyroid is the most common type of endocrine Infrared spectroscopy. Release studies by spectrophotometric malignancy. Incidence of Ca thyroid in India is 11 - 35 per million analysis demonstrated the amount of labeled DMSA released from populations. This disease is more common among females (2 to 3 the microspheres. The effect of poly ethylene glycol (PEG) was time more than in males). It is disease of middle and old age with also studied as PEG alters the surface properties of microspheres. gradual increase in incidence rate with age. Many groups have Glioma cell were incubated with 188Re(V) DMSA - microspheres conducted studies since 1937 on the uptake of radioactive iodine in 96 well plate to study the dose effect. The viability, that is, by the carcinoma of the thyroid and its secondaries before and survival fractions were studied by MTT (Di- methyl thiazol di after surgery and also on the short and long term effects of phenyltetrazolium bromide) assay. The glioma cells were radioiodine on the human body. All these studies have incubated with different doses of 188Re(V) DMSA microspheres conclusively established the use of I-131 as the treatment of choice between 0 and 200 Gy in 20 Gy increments. MTT was reduced in for residual, well differentiated thyroid ca after surgery. the presence of mitochondrial dehydrogenase in living glioma One hundred and fifty-five post surgical patients of different types cells and formed insoluble blue colored formazan crystals. The of Carcinoma of the Thyroid treated between January 1998 and optical density of formazan correlates well with the proportion of August 2004 were taken up in this study. There were 109 (70%) viable cells in the well. The measurements were recorded at females and 46 (30%) males in the age group between 15 and 79 different time point till 120 h of incubation of glioma cells with years. Majority of the patients (121 78%) fell in the age group 188 Re(V) DMSA microspheres. PEG coated, uncoated and of between 20 and 60 years. With our past experience we did not varied sized microspheres encapsulated with 99mTc(V) DMSA resort to low dose ablation advocated by certain groups. 149 were injected in rats for biodistribution studies. (96%) patients fell in the differentiated group. Of these, 119 Microspheres size ranged between 200 nm and 20 µm. DSC (77%) patients had Papillary Carcinoma. 135 (87%) patients were World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 39. S-33 Abstracts: ICRT-2005 administered ablative doses of upto 100 mCi (3.7 GBq). Only 042-IND those patients with multiple metastases were administered doses Impact of FDG-PET imaging in the treatment of between 100 and 300 mCi (3.7-11.1 GBq). Two patients received Lymphomas: Indian experience total doses of more than 1 Ci (37 GBq). Two of the patients were Krishna BA not administered any dose of Radioiodine 131 post surgically. Department of Nuclear Medicine, P.D. Hinduja National Hospital, The follow up period varied between eight months and seven Mahim, Mumbai, India years. One hundred and twenty-nine (83%) patients needed a single dose for successful ablation of the residual thyroid tissue. Abstract not received 16 (10%) patients needed a second dose. Most of the other patients had multiple metastases at the time of diagnosis and hence needed 043-IND three or more doses for ablation of residual thyroid tissue and Treatment of differentiated thyroid cancer using treatment of metastases. Seven patients died during the period of Recombinant TSH injection review. 5 of them died due to causes directly related to Ca Thyroid Krishna BA or its consequences, thus giving a death rate of about 3%. All of Department of Nuclear Medicine, P.D. Hinduja National Hospital, them had either extensive local or distant metastases. This study Mahim, Mumbai, India reveals that almost all the patients are successfully ablated with doses upto 100 mCi (3.7 GBq) of 131I. Although, treatment of Abstract not received metastases was incomplete, we could control the disease in most of these cases. Survival rate was as high as 97% in our series at the end of seven years. Hence we recommend post surgical ablation of the residual thyroid followed by long term follow up of all cancer thyroid patients, including Anaplastic Ca. 041-IND Comparison of Musculo-Skeletal Usg And Radionuclide Soft Tissue Scintigraphy in The Evaluation, Selection and Follow- up of Patients for Radiosynoviorthesis Ray S, Basak B, Dey NR, Sharma SK Eco Nuclear Imaging Centre, Calcutta, India The main objective of this study was to compare and correlate the information obtained from high resolution ultrasound (USG) and soft tissue scintigraphy in the evaluation of painful joint disorders and follow-up of patients after Radiosynoviorthesis. Thirty-two patients suffering from painful joint disorders including Rheumatoid Arthritis were prospectively studied. High resolution ultrasonography of joints was performed with a 15 MHz transducer. Soft tissue scintigraphy of joints were performed in a single head gamma camera with leap collimator 15-20 minutes after injecting 20-25 mCi of Tc-99m MDP. Anterior, posterior, lateral and if needed oblique views were obtained. Delayed images of joints were also obtained. High resolution USG demonstrated effusion, synovial proliferation, thickening, Backer's cyst and bone erosion effectively, and was very useful in guiding aspiration. On the other hand soft tissue scintigraphy was found to be more sensitive in detecting active synovial inflammation and showed excellent correlation with clinical features. The earliest changes after therapy were reduction in the intensity of uptake in soft tissue scintigraphy and reduction of degree of effusion in USG. Delayed phase bone scans were helpful for assessment of extent and severity of disease and deformity. We conclude that soft tissue scintigraphy is a better indicator of the active synovial inflammation having better correlation with clinical features. Hence it is better suited for selecting patients for radiosynoviorthesis. Ultrasound however was found to be a better tool for detecting and treating associated effusion. The earliest changes of treatment response were changes in soft tissue uptake and reduction of effusion World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 40. S-34 Abstracts: ICRT-2005 044-IND despite multiple doses of I-131 (TMD of 442.7 mCi). 33.3% Our Experience of High Dose I-131 Therapy in 75 patients patients with lung metastasis died before the end of 5 years. Only with Well Differentiated Carcinoma Thyroid Followed Up bone MD had slightly better prognosis than either lung or lung Over 5 years plus bone metastasis. Lymph node involvement did not increase Dougall P, Kumar A, Ashok P, Chinwan BP, Khan B, Pandey D, the mortality, and it remained zero at 5 years. Joshi ND. Sitaram Bhartia Institute of Science & Research, New Delhi, India 045-IND Air Monitoring in Radioiodine Therapy Ward Thyroid cancer is the most common endocrine malignancy. The Sarika, Pant GS, Bal CS epidemiology of thyroid cancer is variable, depending on the Department of Nuclear Medicine, All India Institute of Medical geographic location of the patient population. Well differentiated Sciences, New Delhi, India-110024. thyroid cancer (WTC), is responsive to high dose I-131 treatment, and is the most accepted form of therapy, even though the dose In Radioiodine therapy wards, in general the radiation exposure administered for ablation of residual thyroid tissue maybe due to air borne activity from patients administered with 925MBq- controversial. 7.4GBq (25-200mCi) of 131I has to be kept under regulatory limits. At our centre, 75 patients of WTC, mean age 42.4 years, 22 males The purpose of conducting an air monitoring in our setup was to & 53 females (M:F 1:2.4), were treated with high dose oral I-131 assess air borne activity levels. If the levels are high then it may therapy with a Total Mean Dose (TMD) of 263.6 mCi, 4 - 6 weeks lead to increased exposure to the occupational workers and post thyroidectomy. They were followed up over a period of 6 patient's attendants. A total of 22.2GBq (600 mCi) 131I is years. administered every week to our patients in the isolation ward. Twenty ( 26.7%) patients had follicular cancer (FC), 47 (62.7%) After administered of 131I in the dose administration room, patients papillary cancer (PC) and 8 (10.7%) were mixed (MC), on occupy their respective beds. The isolation beds are provided with histopathology, at presentation. 38 (50.7%) patients had only attached toilet facility. Six air samples were collected from residual thyroid tissue (RTT) on I-131 whole body bone scan various regions (high dose room, low dose room, dose (WBS) and 37 (49.3%) presented with metastatic disease (MD) at administration room, special room, corridor and entrance) in the the time of therapy (Table-1). Of the 37 patients with MD, 21 vaccumized vials (9 ml) using 16 G needle at the breathing zone level. One control sample was also collected from the area with no Papillary Follicular Mixed Total possible 131I air-contamination. The vials were then counted in the Residual tissue 28 (59.6%) 5 (25%) 5 (62.5%) 38 (50.7%) pre-calibrated NaI well counter (known efficiency). Metastatic 19 ((40.4%) 15 (75%) 3 (37.5%) 37 (49.3%) The maximum air borne radioiodine concentration was found to Total 47 (62.7%) 20 (26.7%) 8 (10.7%) 75 be 1.999X10-6 ?Ci/cm3 in the high dose room (which keeps on Table 1 Histopathology of disease in the study population decreasing with time, being maximum on second day and zero on Lymph nodes Lung Bone Bone & lung Lung & third and subsequent days). We measured the thyroid counts of the Lymph node staff and patient's attendants, routinely. The estimated thyroid Papillary (15)+2 (2) - - (2) Follicular (1)+3 (4)+5 (3)+3+1(LN) (3) (2) activity never showed any significant increase in the thyroid Mixed (5)+2 - (1) - (1) uptake of the staff and patient's attendants. Total 21 (56.8%) 6 (16.2%) 4 (10.8%) 3 (8.1%) 4 (10.8%) In our setup, air monitoring is strictly followed and performed ( ) single organ involvement + additional organ involvement Table 2 Distribution of metastatic disease in the study population periodically. We conclude that air monitoring program is only one element of the comprehensive radiation protection program and (56.8%) had metastases to the lymph nodes, 6 (16.2%) to the should be a made mandatory practice. lungs, 4 (10.8%) to bone, 3 (8.1%) to bone and lung, and 4 (10.8%) to lung plus lymph nodes (Table-2). Twenty-three patients (7 FC , 046-IND 13 - PC & 3 MC; 6 RTT, 17 - MD) , received more than one dose of Incidence of Micronuclei as Biological Dosimetry in I-131 with a TMD of 422.7 mCi (Range 88 1590 mCi ). 52 Differentiated Thyroid Carcinoma Patients Treated With 131I patients (13 FC, 34 PC, 5 MC; 20 MD and 32 RTT) received a Senthamizhchelvan S1, Pant GS1, Bal Cs1, Malhotra A1, Julka PK2, single TMD of 104.4 (Range 39.5 219 mCi) (Table-3). Nair O2, Rath GK2 Dose Follicular Papillary Mixed RTT MD TMD 1 Department of Nuclear Medicine, 2Department of Radiotherapy, Single 13 p 34 p 5p 32 p 20 p 104.4 mCi All India Institute of Medical Sciences, New Delhi, India. Multiple 7p 13 p 3p 6p 17 p 422.7 mCi 20 p 47 p 8p 38 p 37 p The aim of this study was to estimate the cytogentic damage to Table 3 Number of patients administered single / multiple I-131 Dose peripheral blood lymphocytes based on the incidence of On follow-up, 3 patients of FC with MD (2 lung metastasis and 1 micronuclei in 15 patients receiving radioiodine treatment for with extensive lymph node metastasis), died within 3 months 2 differentiated thyroid cancer. years of therapy. 3 patients of MD (2 FC, 1-MC; 2 bone metastasis Blood samples (2ml) were taken from 15 differentiated thyroid and 1 bone with lung metastasis) died after 5 .5 years, Of the 6 carcinoma patients (2men, 13women; mean age 34y; range,18- patients who died, 5 were FC and only 1 was MC. 2 patients with 52y) immediately before and after their radioiodine therapy. The MD to lungs and bone had received a single dose and were lost to administered activity varied from 925-5550MBq (25-150mCi). follow up. All patients with PC and FC with only RTT, were Whole blood lymphocyte cultures were set up for micronuclei surviving at the end of 5 years. None of the patients with MD to assay consisting of 0.5ml of whole blood, 10g/ml of PHA-M, 10% lymph nodes died at the end of 5 years, either receiving single or fetal bovine serum. Cultures were incubated at 37C for 72hrs, with multiple doses. In our study group, the TMD for ablation used in last 26hrs in presence of 6g/ml cytochalasin -B (Cyt-B) to arrest RTT was 100.4mCi, and 5 year mortality was zero. The patients the cells at cytokinesis after the nuclear division is completed. with MD involving lungs and bone had the worst prognosis, Cultures were terminated and harvested after 72hrs using standard World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 41. S-35 Abstracts: ICRT-2005 protocol and cells were spread in glass slides for staining and post surgery. 51 patients ( 6 with nodal metastasis ) received 1.85 analysis. Micronuclei were scored in 1000 cytokinesis blocked GBq (50mCi) and 13 patients received 5.55 GBq ( 150mCi) as (CB) cells for each sample. The effective total body dose (ETBD) ablative dose in a non randomized manner (group 1 and group 2 ). was estimated for all patients from previously obtained in vitro In the first group, 14/51 patients are awaiting their first follow up Co-60 dose- response curve. scan and thus not included in the analysis at this point of time. Out The incidence of micronuclei before and after therapy was 198 of the 37 patients, 24 (65%) achieved total ablation and 10 (27%) (mean S.D) and 3210 (mean S.D) respectively. The ETBD in near total ablation.Significant persistent remnant tissue was seen these patients ranged from 16.3 33.8 mGy (mean S.D; 21.54.8). in 3 (8%) cases and required a second ablative dose. 29/37 had an The negligible amount of cytogenetic damage to peripheral blood average follow up of 22 months. 1 case of ipsilateral neck lymphocytes could be due to low iodine uptake, the small size of recurrence was seen. In group two, 13 patients (7 with lymph node remnant tissue and rapid washout of 131I from the body in thyroid metastasis) received 5.55 GBq (150mCi). A single dose was carcinoma patients. Relatively low incidence of micronuclei after adequate to ablate the residual tissue with an average 23 months radioiodine therapy in this study as compared to external disease free interval. In group three, 14 patients showed evidence radiotherapy, reveals that there is less radiation risk/detriment to of residual tissue plus lymph node metastasis in the radioiodine ca-thyroid patients treated with 131I. scan. These patients received a higher dose ranging from 5.55- 7.40 GBq (150-200mCi).There was no fixed criteria for selection 047-IND of a particular dose. 8/14 (57%) in this group required more than Optimizing the Indications for Radioiodine Therapy as an one treatment dose of radioiodine. Adjuvant Treatment in Differentiated Thyroid Carcinoma. The above results show that 1.85 GBq of I131 is adequate to achieve Choudhury PS1, Dewan AK2 desired remnant ablation and an extended disease free outcome in Departments of Nuclear Medicine1 & Surgical Oncology2, Rajiv the presence of only residual thyroid tissue post operatively. An Gandhi Cancer Institute & Research Centre, New-Delhi, India I131 scan appears to be the single most important factor for deciding the ablative dose in this group of patients irrespective of the Radioiodine (I131) therapy as an adjuvant treatment in post surgical presence or absence of nodal disease during primary treatment. At management of differentiated thyroid cancer is generally this stage there appears to be no difference in the outcome of performed for achieving two intended objectives: to increase the patients receiving low or high ablative dose in the above patient specificity & positive predictive value of subsequent radio iodine population. Whether there is a difference in the time to recurrence scanning and serum thyroglobulin measurements for detection of in these two different groups will need to be seen with a longer recurrent or metastatic disease and to destroy any residual albeit followup period . Evidence of nodal metastasis in the radio iodine undetected microscopic foci of malignant disease. Although it is scan generally preempts the need for higher and multiple more or less agreed that adjuvant treatment of differentiated radioactive iodine dose. thyroid cancer is required in most of the patients, the factors influencing optimum effective dose to achieve remnant ablation 048-IND and at the same time reduce the chance of recurrence has not been Radioactive Iodine (I-131) in the Treatment of well established. The current practice is to use either a low fixed Hyperthyroidism in Hilly Terrains an Initial Experience dose for low risk group or a higher dose for the high risk group Sood A, Seam RK (based on clinical presentation, surgical and histopathological Nuclear Medicine Centre, Regional Cancer Centre, Indira Gandhi findings) or follow the dosimetric method of calculating the Medical College, Shimla-171001, INDIA ablative dose. In this paper we have made an attempt to optimize the indictions and ablative radioiodine dose as an adjuvant We present our initial experience of treating patients of treatment in differentiated thyroid carcinoma. hyperthyroidism with radioactive iodine (RAI) in the hilly area of Patients of differentiated thyroid carcinoma who underwent India, which falls, under endemic zone of iodine deficiency (sub adjuvant treatment with radioiodine, in the last 5 years, were Himalayan zone). People here have largely switched over to analysed. Patients with less than 12 months followup, iodized salt to supplement the iodine intake in the food. It has extrathyroidal extension seen per operatively or shown remarkable regression in goitre and thyroid disorders. histopathologically and with evidence of distant metastasis at RAI (I-131) has been in use successfully for more than 60 years for presentation were excluded from this study. the treatment of hyperthyroidism that may be due to Graves' The patients were divided into three groups as per the dose of I131 disease (diffuse toxic goitre), toxic multi nodular goitre or solitary received as adjuvant treatment (1.85 GBq, 5.55 GBq & > 5.55 toxic nodule. After the treatment with I-131, these patients are GBq). The end points were adequacy of remnant ablation and the followed up at interval of 6 & 12 weeks initially followed by 3 outcome at the average followup period . Ablation was defined as months for the first year and then 6-12 months henceforth. This is total; near total or partial based on the findings of first followup the only facility to treat patients of thyrotoxicosis with RAI in our scan 6 months post treatment. The outcome was evaluated by area. Physicians used to treat such patients with drugs or surgery clinical examination; serum thyroglobulin estimation and I131 scan before the availability of RAI (I-131). But with availability of the (after withdrawal of thyroxine) at subsequent follow up at an facility for administering RAI since mid 2000 and increased interval of 6 months. The status at follow up was based on all the awareness regarding its advantage of definite treatment, low cost, above three findings. No gold standard was defined. A total of 78 and easy administration with better compliance in hilly area where patients were analysed. Age range was 17-72 yrs with an average regular follow-up and cost are quite consideration, has made it age of 38 years & a female preponderance (62%). 77% of patients quite popular among the referring doctors. had papillary carcinoma, 8% follicular carcinoma & the rest was In our centre emphasis was made on the treatment options of mixed variety. 64 patients showed evidence of residual tissue available to doctors and patients explaining the advantages vs. only in the post operative radioiodine scan. 20% (13/64) of these disadvantages for the various modalities. The objective of this patients had histopathological evidence of lymph node metastasis abstract is to show the outcome of treatment given to patients since World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 42. S-36 Abstracts: ICRT-2005 so far. Metaiodobenzylguanidine (MIBG) labeled with I-131 is used for Total 108 patients referred for RAI treatment have been treated so imaging neural crest derived tumors like pheochromocytoma and far from August 2000 till March 2005 with 136 doses administered neuroblastoma as well as for the scintigraphic assessment of which consisted of 22 males and 86 females with age range from cardiac sympathetic neuronal integrity. Different methods of 28-64 yrs (mean age-43.1 yrs) and 19-70 yrs (mean age- 42.7 yrs) preparations of MIBG labeling with I-131 are available with respectively. 87 patients were given single dose, while 21 patients variable success. In the present study we tried to label MIBG using required 2 or more doses to achieve euthyroid status. Re-treatment ammonium sulphate facilitated exchange method. was done not before 3 months after first administration if there was The radiolabeling procedure was based on ammonium sulphate evidence of residual disease on clinical and biochemical status. 15 facilitated exchange radioiodination of MIBG in an aqueous of the 108 patients were excluded from this study, as their follow solution in a closed system. The radioactive yield of I-131 MIBG up period was less than 3 months. Remaining 93 patients was found to be more than 90 % which was achieved in 30 minutes underwent regular follow-ups. 33 out of these 93 patients at 160-170 C. The concentration range of MIBG and ammonium developed hypothyroidism during the period ranging from 2.5 sulphate was in the ratio of 1:10. Radiochemical purity, purity and months to 42 months post RAI administration (35.5%). Majority stability of the labeled MIBG were checked. of them (28/33) developed hypothyroidism with in 1 yr of post The reaction mixture was subjected to purification over an anion RAI (84.4%) while remaining developed hypothyroidism after 1 exchange column (Dowex-1 X 8,200-400 mesh, Cl- form yr. Earliest appearance of hypothyroidism in patient was at 3 preconditioned with 4M HCl). RCP was checked by paper months that were promptly treated with L-thyroxin. Average chromatography using Whatmann 1 and different solvent systems amount of iodine-131 /dose given was 6.2 mCi. Doses of RAI (I- and found to be more than 98%. Stability of I-131 MIBG was 131) administered ranged from 3.3 mCi (minimum) to 20 mCi checked by adding 1% benzyl alcohol and preparation was found (maximum) in different patients during the course of treatment. to be stable for four days. All these patients are still undergoing periodic follow-up without These results show that I-131 MIBG can be prepared easily and any significant side effect. The result of this study shows that I-131 rapidly using ammonium sulphate facilitated exchange method is safe and cost effective method to treat hyperthyroidism. for diagnostic purpose. Because of simplicity of the method, it can be utilized in Nuclear Medicine Centers in developing countries. 049-IND Evaluation of Medullary Thyroid Carcinoma 051-IND Dr. R. Krishnakumar Tele Consultation and Tele Follow up of Thyroid Cancer Department of Nuclear Medicine, Cancer Institute (WIA), Patients a Pilot Study Chennai-600020, India, Pradhan PK, Das BK, Mohanty BN, Mishra SK Dept. of Nuclear Medicine and Dept. of Endocrine Surgery, Medullary thyroid Carcinoma (MTC) originates in para-follicular SGPGIMS, Lucknow and Dept. of Experimental Surgery, S.C.B cells in thyroid and belongs to the APUDOMA group of Medical college, Cuttack, INDIA neuroendocrine tumors. It can be hereditary or sporadic variety. Hereditary variety can present in 3 forms namely-MEN II A, MEN Radioiodine therapy is an essential component of thyroid cancer II B and familial forms. All three forms have RET proto oncogene management and these patients require life long follow up at timed mutation. MEN II A include MTC, Pheochromocytoma and interval. Though radioiodine therapy is a well established Hyperparathyroidism. MTC, Pheochromocytoma, multiple adjuvant treatment for well differentiated thyroid cancer, still the mucosal neuromas and ganglioneuromatosis of G.I.tract acceptance by the surgical colleagues and patients is not uniform. constitute MEN II B with marfanoid faeatures. We routinely In addition, this facility is not available in the eastern part of the exclude Pheochromocytoma by doing CT or US evaluation of country. Therefore, such patients are required to travel more than abdomen with Urinary catecholamine estimation.To rule out 1500 K.M. to avail this treatment and subsequent follow up at our familial variety we doing serum calcitonin for the siblings and also Institution. The existing telemedicine facility between SGPGIMS, for children.The standard treatment for MTC is total Lucknow and SCB Medical College, Cuttack provided the thyroidectomy (TT) with or without Radical neck dissection opportunity to utilise the system for tele-consultation and tele- depending on the individual caess.We evaluate these MTC with follow up of thyroid cancer patients. Tc99m DMSA(V) scans 3-4 weeks after TT . Serum Calcitonin is The rationale of this ongoing study is to evaluate the suitability of estimated and this is correlated with DMSA findings. If DMSA is telemedicine for tele consultation prior to radioiodine therapy and abnormal the finding is correlated with regional CT sacn / bone tele follow up following radioiodine therapy of patients with well scan. If lesion is found suitable the same is resected. Serum differentiated thyroid cancer. Calcitonin estimation forms the sheet anchor during follow-up of Thirty patients ( 10 new cases and 20 follow up cases) were these patients. Whenever it is elevated DMSA scan is done. There included in this study. New cases were studied on the basis of case is good correlation and high sensitivity between Calcitonin and history inputs by the operating surgeon and direct patient DMSA findings. In few instances I131 MIBG scan were also done. consultation to find out their suitability for high dose radioiodine Our experience in the past 5 years with about 25 patients are therapy. At the same time pre-therapy instructions as well as discussed. details of admission were finalised. Follow up of patients( 20 in number ) were discussed and examined on live along with 050-IND operating surgeon with respect to compliance of thyroxine A Single Vial Method of Preparation of I-131 Meta- suppression therapy, local recurrence and need for further high iodobenzylguanidine (MIBG) dose radioiodine therapy. Each time, at least one surgeon and Snehlata, Tripathy M, Malhotra A nuclear physician were involved during live evaluation of patients Department of Nuclear Medicine, All India Institute of Medical which was done with VSAT, broad band of 256 Kbps band width Sciences, New Delhi, India. provided by ISRO, Bangalore, India and case history, radiological World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 43. S-37 Abstracts: ICRT-2005 and nuclear medicine images were already transmitted prior to Graves' hyperthyroidism (n = 59) who had not been previously live evaluation. treated with radioactive iodine were randomized in two groups of All ten new cases were found to be suitable for high dose 185 MBq (5 Ci) and 370MBq (10 mCi). l patients were followed radioiodine therapy. The appointment dates for their evaluation for two years, with 6-month intervals for following clinical and admission could be finalised and instructions for withdrawal outcomes: hyperthyroid requiring further radioiodine, and of thyroxin could be given to patients. Out of twenty follow up hypothyroid requiring life-long replacement therapy. Euthyroid cases, only thirteen patients were required to come to SGPGIMS, and hypothyroid states were considered successful therapy (cure) Lucknow. Rest of the seven patients could be managed with and hyperthyroid state was considered failure (no response or instructions and need not travel to our Institution. relapse). Results: Totally, among 59 patients treated with I-131, 20 Telemedicine has been utilised for follow up of patients in several (33.9%) patients became euthyroid and 19(32.2%) became areas. Gilmour et al emphasised the importance of telemedicine hypothyroid, while failed therapy was noticed in 20 patients for diagnosis and management of dermatology cases referred from (33.9%). In the group treated by 185 MBq (33 patients), primary care. Fifty percent of patients could have been managed 10(30.3%) were euthyroid, 6(18.2%) were hypothyroid (overall by single tele consultation without requirement of further cure rate of 48.5%), while 17(51.5%) remained hyperthyroid by specialist intervention. Alen et al reported the utilisation of the end of the follow-up period. From the 26 patients treated with telemedicine in cancer patients in rural areas. Redlick et al used 370 MBq, the euthyroid and hypothyroid states were observed in telemedicine to evaluate patient and physician satisfaction with 10(38.5%) and 13(50%) patients, respectively (overall cure rate of tele-consultations in follow up of burn cases and to assess the cost 88.5%), and hyperthyroid state in 3(11.5%). No relationship was and benefit of tele-consultations. Patients were very satisfied with noted between the outcome and age, sex, size of the thyroid gland their and thyroid uptake, but the relationship between the disease Tele-consultations and found them more economical and time outcome and the amount of administered radioiodine was efficient than in person visits. Telemedicine technology has been significant (P<0.003).Discussion: Although the incidence rate of utilised for diagnosis of thyroid disorders. However, tele- early hypothyroidism (by the end of 2 years) in the group treated consultation and tele-follow up of thyroid cancer patients before with 185 MBq is less than those treated with 370 MBq, the and after radioiodine therapy has never been utilised as per incidence of failed therapy is higher in the former group. In published literature. This telemedicine tool has strong potential addition, long-term hypothyroidism prevalence is not for consultations of patients with thyroid cancer and monitoring significantly different by using different doses ofI-131. On the them subsequently at timed interval following radioiodine other hand, if the initial dose is so little to cure, cost and time for treatment.In our pilot study 100 % of patients consented and perfect treatment, number of office visits and morbidity due to subsequently received radioiodine and 35 % of follow up patients untreated hyperthyroidism are markedly increased. Conclusion: did not visit our Institution at Lucknow because of live interaction Regarding lower rate of failed therapy with 370 MBq, and as there through telemedicine. is no significant difference in late hypothyroidism between low The tele-consultation and tele-follow up of thyroid cancer patients doses and high doses of I-131, we concluded that 370 MBq is the provided great degree of patient satisfaction because of direct optimal fixed dose for treatment of Graves' disease. audiovisual contact. Saving of travel expenses as well as inconvenience to travel such long distances could be achieved in 053-IRA 35 % of cases. This is substantial both in terms of direct and The Rate of Depression and its Risk Stratification in Patients indirect expenditure as well as loss of working hours for the With Differentiated Thyroid Cancers Treated With accompanying persons as prevails in our society. The satisfaction Radioactive Iodine of the operating surgeon could be achieved by discussing Eftekhari M, Fallahi B, Ansari S, Izadian ES, Esfahani AF, Beiki individual cases with regards to further follow up and D, Saghari M management. Research Institute for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran 052-IRA Comparative Evaluation of the Two Fixed Dose Methods of Depression is a common disease in general population and may be Radioiodine Therapy (185 MBq and 370 MBq) for the more frequent in the cases of malignant diseases. Diagnosis and Treatment of Graves' Disease. treatment of depressions in such patients may improve the quality Esfahani AF, Fallahi B, Kakhki VRD, Eftekhari M, Beiki D, of life. The aim of this study was to determine the risk of Saghari M depression in patients diagnosed as differentiated thyroid cancers Research Institute for nuclear medicine, Shariati Hospital, Tehran (DTC) and treated with radioactive iodine (131I). University of Medical Sciences, Tehran, I.R. Iran In a historical Cohort study, 390 DTC patients, 312 female and 78 male, 18-68 years with median age of 41 years who were treated Radioiodine therapy is the safest, simplest, least expensive and with 131I and 390 control cases selected from the patients' relatives most effective method for treatment of Graves' disease. But and matched with DTC cases by age, sex, wedding state and socio- optimal method for determining iodine-131 treatment doses for economic status were entered the study. Each patient and his/her Graves' hyperthyroidism is unknown, and techniques have varied control were concurrently assessed with Beck's questionnaire for from a fixed dose to more elaborate calculations based upon gland diagnosis of depression. The data was analyzed to detect the rate, size, iodine uptake, and iodine turnover. Due to difficulties in severity and relative risk of depression and the effect of some previous methods for dose determination, fixed dose method of variables on the severity of depression in these patients. I-131 is now considered the best practical method for I-131 Of 390 patients, 179(45.9%) showed some degree of depression, therapy in Graves' disease, but there is no consensus on the dose. 20.3% mild, 14.1% moderate, 11% partially severe and 0.5% We compared two routinely recommended fixed doses of 185 and severe according to Beck score, while the proportional frequency 370 MBq for this purpose. Methods and Materials: Patients with of different grades of depression among the control group was World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 44. S-38 Abstracts: ICRT-2005 15.5% and overall relative risk of depression in DTC patients was to treatment of 100 patients (33 males and 67 females) was 2.96. The frequency of depression in female patients, 47.8% was evaluated by serum TSH, Tg levels and areas of thyroid remnant as lesser than male, 38.5% (p=0.013) and in married female (46.2%) measured by whole body scan with 131I performed 6 months after was greater than single (14.3%) but lesser than divorced or widow therapy. Treatment response was evident by decreased or lack of 131 female patients (82.4%), (p<0.0001). Depression was more I uptake in the thyroid bed and Tg 5 ng/ml. Remnant area was prevalent and more severe in cases of papillary, 47.9% than decreased about 74.5% in females and 75.5% in males. No follicular carcinoma, 33.3% (p=0.014) and also was more significant difference between sex groups was observed. Because predominant in less-educated than in high-educated patients of radiation protection concerns and socioeconomic reasons, (p<0.0001). lower ablations doses of 131I ( 1110 MBq) might be as effective, and In DTC patients with history of radio-iodine therapy, the rate of should be evaluated. depression is almost three times of the general population, so screening and treatment of depression especially in high risk O56-IRA patients like married or divorced female and less-educated Dose Calculations of 186Re For Production and Feasibility of patients may be of great importance for improving the patients' use to Intravascular Brachyherapy After Coronary quality of life. Angioplasty Taghizadeh-asl M1, Pourbeigi H1, Meigooni AS2, Ghahremani 054-IRA AR1, Ghafoorian H1 Strontium-89 in Palliative Treatment of Widespread Painful 1 Department of Nuclear Research Center, Atomic Energy Bone Metastases: Response Rate and Duration Organization of Iran and 2Department of Radiation Medicines, Peiman Haddad MD, Farhad Ghadiri MD University of Kentucky, USA Radiation Oncology Department, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran Feasibility of 186Re production has been studied by 185Re (n,g) 186Re reaction in a Research reactor,. Liquid Scintillation Counter has Intravenous injection of Strontium-89 (Sr-89) is an accepted measured the activity of 186Re-perrhenate about 7.2 mCi/mg at 5 palliative treatment for bone metastases. We evaluated the pain days after end of irradiation. To determine the required specific relief achieved with this radiopharmaceutical in patients with widespread painful bone metastases from prostate and breast activity and possibility of application of 186Re liquid for cancers. intravascular brachytherapy calculation of dose distribution has Pain intensity on a 9-grade scale and use of narcotics was recorded been carried out using MCNP-4b code of Monte Carlo . Depth before and after Sr-89 injection, and the ensuing palliative effect dose rate in 0.5 mm depth of around angioplasty balloon (20mm was divided into complete, partial and no response. The duration length, 3mm diameter) has been calculated that it is 1.152 of response was also recorded. Thirty-five patients with [(cGy/min)/(mCi/ml)]. Suitable specific activity for delivery of widespread painful bone metastases were treated with Sr-89, of doses from 12 to 20 Gy in 4min has been determined, 300 to 400 whom 22 had prostate and 13 breast cancers. Mean follow-up was (mCi/ml). Eighty-two percent of the energy deposited in the first 227 days, during which death was recorded for 32 patients. 0.5mm of vessel wall from the balloon. Therefore there is a little Fourteen patients (40%) had a complete response, 9 (26%) partial non-uniformity in respect to other beta emitter as such as, 90Y and 188 and 12 (34%) no response. In the 23 responding patients, mean W/188Re. Medical internal radiation dosimetry (MIRD) was duration of response was 6 months. In 17 patients the response was calculated assuming that contents had been released into the present until death. There was no significant relationship between system circulation. 186Re DTPA accommodate only kidneys and pain response and patients' age or type of primary cancer. No side bladder specifically, there fore radiation dose of whole body is less effects were recorded other than mild and temporary drop in white than 99mTc-DTPA. We conclude that production of 186Re DTPA blood cell and platelet counts. Three patients with a complete easy by irradiation of enriched 185Re target in a 5MW Research response had a second injection of Sr-89 after progression of pain. Reactor and also 186Re-DTPA is safe to use and suitable for intra- One of these patients had a second partial response; the other 2 did vascular brachytherapy for coronary with centric cross section. not show a response to the second injection. The use of Sr-89 for treatment of widespread painful bone 057-JAP metastases from prostate and breast cancers in our department Effect of Auger Electrons Internalized as Indium-111 Labelled showed a 66% rate of response and a mean response duration of 6 N-MYC Phosphorothionate Antisense Oligonucleotide (In- months, with no significant side effects. 111-N-MYC-AS) on Human Neuroblastoma Cells: In vitro and In vivo studies 055-IRA Watanabe N, Tanada S, SasakiY. Study of ablation efficiency of 3600 MBq of I-131 in the Department of Medical Imaging, National Institute of Treatment of Thyroid Carcinoma Radiological Sciences, Chiba 263-8555, Japan Takavar A, Eftekhari M, Fard-Esfahani A, Beiki D Research Institute for Nuclear Medicine, Shariati Hospital, Auger electrons which enter into cells cause biological effects School of Medicine, Tehran University of Medical Sciences, with high-LET short range radiation on the neighborhood. The Tehran, Iran purpose of this study was to investigate the internalization of In- 111-N-myc-AS and suppression of N-MYC in human The basic question of threshold for the ablation of thyroid remnant neuroblastoma cells. Fifteen-mer AS, which was complementary after surgery remains unanswered. However, radioiodine therapy to the region of the mRNA of N-myc beginning with ATG start is still being used as a standard method of treatment. codon, was derivatized with SCN-Bn-EDTA and labeled with In- In present investigation treatment responses of 100 patients with 111. In-111-N-myc-AS (1.33MBq/nmol) was prepared as naked thyroid cancer treated with 3600 MBq of 131 I is studied. Response form and encapsulated in cationic multilamellar liposome (CML). World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 45. S-39 Abstracts: ICRT-2005 The internalization of In-111-N-myc-AS with or without CML but also for several solid tumors, such as breast cancer. Visual into human neuroblastoma SK-N-DZ cells was determined both in interpretation of PET scans is sufficient for assessment of tumor vitro (cell culture) and in vivo (tumor bearing nude mice) studies response after completion of therapy. However, quantitative by Southern blot analysis. Quantity of N-MYC in the tumor cells analysis is generally required, if PET imaging is used to predict was also measured by Western blot analysis. In in vitro system tumor response early in the course of therapy. 0.69?0.02pmol of In-111-N-myc-AS (80pmol) with CML was FDG PET may become the method of choice for the early internalized in the cells (5X106) by 12h at 4?C, which increased to assessment of treatment response to primary chemotherapy in 8.05?0.43pmol at 37?C. The internalized naked In-111-N-myc- patients with breast cancer. Although about 70-80% of patients AS was 0.58?0.01pmol and 0.92?0.03pmol at 4 and 37?C, show clinical response to primary chemotherapy, the pathological respectively. In vivo study revealed the internalization of In-111- response rate is only in the range of 20-30%. The sensitivity and N-myc-AS (8nmol) with CML in tumor cells (5X106) as specificity to predict complete pathologic response after the first 6.44?0.71pmol, while none (0pmol) of naked In-111-N-myc-AS course of chemotherapy were 90% and 74%, respectively. was internalized. The effect of Auger electrons was shown by a Therefore, as early as after the first course of therapy responding decrease of N-MYC of the tumor cells by 20.6?2.49% in vitro and and non-responding tumors can be differentiated by PET. One 12.9?1.17% in vivo in the case of In-111-N-myc-AS with CML, baseline FDG PET and one scan after the first course of primary whereas unlabeled AS with CML or In-111-phosphorothioate chemotherapy seems to be sufficient to identify non-responders at sense oligonucleotide did not decrease the quantity of N-MYC of an early stage of therapy. By a threshold defined as a decrease the tumor cells in vitro or in vivo. In conclusion, In-111-N-myc- below 55%, compared to the baseline scan, all responders were AS with CML could be internalized into human neuroblastoma correctly identified after the first course (sensitivity 100%, cells and suppress the activity of N-myc gene, which may prove specificity 85%). FDG PET may be helpful for improving patient useful for targeted Auger electrons radiotherapy. management (30-40%) by avoiding ineffective chemotherapy and unnecessary side effects 058-KOR FDG PET can also be useful for prediction of response to The Role of PET in Monitoring Therapeutic Response hormonal therapy. In one study which investigated biological Lee MC. Department of Nuclear Medicine, Seoul, Korea tumor characteristics like glucose metabolism and perfusion, determined with dynamic FDG PET and 15O-water PET before PET and PET/CT are the fastest growing imaging modalities any therapy concluded that PET could predict the response to neo- worldwide. PET technology has already become an important adjuvant chemotherapy. The high pretreatment metabolic rate for diagnostic tool for staging disease, evaluating the treatment FDG predicted a poor response to therapy and a low metabolic rate effects and the long-term follow-up of cancer patients in relative to blood flow was found to be a predictor of complete developed nations. In summary, PET/CT studies can affect the response patient management in about 25-30% of the oncological patients. The most useful indication of FDG-PET in cancer patients is the 059-LAT differentiation between recurrence and post-therapy changes. I-131 Therapy for Euthyroid Goiter in Latvia. Responses to therapy can be identified earlier and with greater Berzina A, Berzina D, Roznere L, Vevere I accuracy than is possible with anatomic imaging modalities. Latvian Ocology Centre Prognostic information available through 18F-FDG PET is superior to that of conventional imaging for many cancers. The I-131 therapy for thyroid cancer and hyperthyroidism is used since sensitivity and specificity of FDG-PET in detecting recurrence 1964 in Latvia, but for patients with euthyroid nodular or diffuse amounted to 94% and 92% respectively. On the contrary, the goiter only since 1995. sensitivity and specificity of conventional images were only 78% The aim of this study was to analyse 5 year statistics and to inform and 68%. FDG-PET is increasingly used to monitor tumor doctors about possibilities of such therapy method in Latvia. In response in patients undergoing chemotherapy, chemo- between 1995-2000 in Latvian Oncology Centre 75 patients with radiotherapy and radiopharmaceutical therapy. 18F-FDG PET is euthyroid goiter were treated with I-131. Radiation dose for an accurate study for differentiating residual viable tumor tissue thyroid volume was 100-150 Gy. Patients with goiter volume from therapy-induced fibrosis. It may allow the prediction of >100 ml and with tracheal compression received radiation dose 50 tumor response and patient outcome very early in the course of Gy 2 or 3 times. There were 25 patients with recurrent goiter after therapy. Overall survival and progression-free survival are surgery, 50 patients has increased surgical risk because of other correlated highly significantly with metabolic responders in PET. severe diseases or retrosternal localization of goiter. In one paper, the median progression-free survival of metabolic Our results demonstrated that 6 month after I-131 therapy there non-responders was only 1.8 months but that of metabolic was reduction of goiter volume by 20% in 38 cases, by 30% in 19 responders was 5.9 months. In patients without a significant cases and by 50% in 11 cases. In 7 cases there was no reduction of change in tumor 18F-FDG uptake, the treatment change should be goiter volume, but the growing of goiter was stopped (follow up 4 considered early in the course of therapy. years). In patients with solid tumors treated by preoperative We conclude that I-131 therapy is effective for reducing of chemotherapy, a change in 18F-FDG uptake of 35%-50% within thyroid goiter volume and is used in Latvia (20-25 patients per the initial weeks of chemotherapy has been found to provide the year). If the aim of I-131 therapy is not only to reduce the hyper highest accuracy for the prediction of histopahologically complete function of nodular goiter, but also to reduce the goiter volume, the response. Early identification of non-responding patients is of suppression of TSH is not compulsory. great clinical importance. Effective chemotherapy causes a marked decrease in tumor 18F-FDG uptake (15-40%) within 1-3 wk after the initiation of therapy. This has been extensively investigated for malignant lymphomas, World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 46. S-40 Abstracts: ICRT-2005 060-LIT treatment thyroid volume (40±18 ml vs 18.4±11 ml) and was Is it Worth to Calculate the Dose of Radioiodine? given for persistent hyperthyroidism after a mean of 13 months Mikalauskas V1, Kuprionis G1, Vajauskas D2 (minimum 3 months, maximum 34 months). Not sufficient first 1Department of Nuclear Medicine, Kaunas Medical University target dose was delivered to the thyroid due to Lithuanian Hospital, Lithuania and 2Kaunas Medical University, Lithuania regulations as mentioned before. The third treatment of 120 and 142 Gy was given in four and nine months in two cases. Administration of empirical doses of radioiodine (RAI) has been We concluded that therapeutic success was associated with preferred to calculated doses in many hospitals, because the need calculation of individual target dose adjusted to the thyroid to measure the size and the iodine uptake in the thyroid involves uptake, volume and the cause of hyperthyroidism in each patient. considerable inconvenience to the patient and additional costs. The preparation of RAI of varying activities also means extra 061-LIT work. Today there is no general consensus on whether radioiodine Somatostatin Receptor Imaging and Therapy an Ever should be given as a fixed dose or should be calculated. There is Expanding Choice also no consensus regarding the question of which radiation Kulakiene I, Warbey VS, Buscombe JR, Hilson AJW burden should be administered to a given volume of thyroid if the Dept of Nuclear Medicine, Royal Free Hospital, London, UK activity is calculated. However, while it is possible to deliver a relatively precise dose of radiation to the thyroid gland, maybe it is Cells express a variety of different receptor proteins on their worth doing this? surface, some of which have a high affinity for regulatory The aim of this study was to investigate the results of different peptides, such as somatostatin. Somatostatin receptors (SSTR) are uptake and volume dependent target doses on clinical outcome of over-expressed in several human tumours, especially those of patients with hyperthyroidism in Graves' disease, multi-nodular neuroendocrine origin. The biological effects of SSTR are toxic goiter or toxic adenoma after radioiodine therapy. mediated by five specific receptor subtypes (SSTR 1-5) to which We reviewed the records of 428 patients (389 women and 39 men, the native peptide binds. However, somatostatin analogues have mean age 56.8±12.9 years) who had received radioiodine major differences in their affinities for different receptor subtypes. treatment for Graves' disease and multinodular toxic goiter DTPA-octreotide binds with reasonably high affinity to SSTR 2 (n=312) or toxic adenoma (n=116) during the period of 2000-2004 and with low affinity to SSTR 5. RC-160 has enhanced binding in Kaunas Medical University Hospital. Most patients were given affinity to SSTR 4, while depreotide preferentially binds to SSTR antithyroid drug therapy in order to achieve euthyroidism before 2, 3 and 5. DOTA-lanreotide binds to SSTR 2, 3, 4 and 5 with high treatment with RAI. Radioiodine uptake test with repeated affinity, and to SSTR 1 with low affinity. DOTA-Tyr3-octreotate measurements at 2, 6, 24, 48 and/or 72 and/or 96 hr to define the exhibits the highest affinity for SSTR 2. Somatostatin analogues effective half-life was performed. In addition, all the patients labelled with a variety of gamma-, positron- and beta-emitters, are underwent thyroid ultrasonography and scintigraphy to define the becoming of increasing interest in tumour targeting for either the volume of the thyroid. The 131I activities were calculated localization or the targeted radiotherapy of neoplasms. according to the formula of Marinelli. In addition to the normal The aim of this study was to evaluate the use of 99mTc-depreotide in calculation individual target doses were adjusted to the thyroid visualisation of neuroendocrine tumours and other tumours volumes of each patient before therapy. For statistical evaluation, expressing somatostatin receptors, when 111In-pentetreotide and/or the patients were divided into four groups: group I included those 123 I-MIBG scans were negative or inconclusive and to choose a with a thyroid volume <15 ml before therapy, group II included suitable radiopharmaceutical for targeted therapy. those ranging from a 15-25 ml, group III included those ranging The case records of 23 patients (17 women and 6 men, mean age from a 26-50 ml and group IV included those with thyroid 56.78 range 26-78) who underwent 99mTc-depreotide scans over volumes >51 ml. Statistical analysis was performed using SPSS the period from January 2004 to March 2005 were reviewed. for Windows, version 12.0. A p-value less than 0.05 was Fourteen patients presented with neuroendocrine tumours, 2 with considered statistically significant. Merkel cell tumours, 2 with thymic carcinomas, 3 with medullary The mean effective half-life for thyroid gland in all patient groups and 1 with papillary carcinoma of the thyroid. Two patients had was 5.32 days and there was no significant difference between the previous 90Y-DOTA-lanreotide, one 131I-MIBG and one 153Sm- groups. Patients with Graves' disease and multinodular toxic EDTMP therapy. Whole body imaging was performed with goiter in group I (n=42) received a target dose of 124.87±15 Gy, in tomography of the liver at 1 and 4 hours after intravenous injection group II (n=77) - 128.35±10 Gy, in group III (n=153) - 124.29±22 of 700-750 MBq of 99mTc-depreotide. 21/23 patients had 111In- Gy. But, the patients in group IV (n=29) received a target dose of pentetreotide whole-body scintigraphy with tomography of the only 103.74±35 Gy, because the administered activity of 131I for upper abdomen. Twelve of these patients also had 123I-MIBG outpatients is limited to 400 MBq according to the Lithuanian imaging. 2/23 had 18F-FDG-PET scans which were negative. One regulations. In subgroup of patients with toxic adenoma an experienced reader reviewed all the scans and compared uptake activity was calculated to deliver 140 and 160 Gy for the treatment between the tracers. in group I (n=72) and in group II accordingly. Received target dose Results showed that 99mTc-depreotide imaging demonstrated in this subset of patients was in group I 156.19±20 Gy and in group positive findings in 19 cases (82.6%) and was superior to 111In- II (n=38) - 158.19±22 Gy. pentetreotide imaging in 15 cases and PET in 2 cases. In 2 cases Administration of a single dose of RAI resulted in the control of 111 In-pentetreotide was better than 99mTc-depreotide. 123I-MIBG hyperthyroidism in 91.8% of patients. Unfortunately 35 (8.2%) scintigraphy was positive only in two cases. All three imaging patients with Graves' disease required the second and two of them modalities were negative in 2 cases. One patient had two the third RAI treatment to achieve either a hypothyroid or a populations of tumour cells, presenting with different pattern of euthyroid state. The second target dose was significantly higher uptake on depreotide, pentetreotide and MIBG scan. According to (p<0.05) than the first (128±25 Gy vs 119.8±24 Gy) because was the intensity of uptake different possible treatments were adjusted to the significantly reduced (p<0.05) after the first recommended: in 5 cases 90Y-DOTA-lanreotide, in 1 case 131I- World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 47. S-41 Abstracts: ICRT-2005 MIBG and in 1 case intra-arterial treatment with 90Y-sirspheres for groups were prescribed beta blockers for 4-6 weeks. Average radio wide spread liver metastases. iodine dose in both groups was 5 ± 0.92 mCi. All patients were We conclude that 99mTc-depreotide scintigraphy is a very evaluated both clinically and bio chemically 3, 6, 12 months after promising method in the visualisation of somatostatin receptor the radio iodine application. The duration to achieve euthyroid expressing tumours and in patient selection for the targeted state, patient tolerance and side effects if any were meticulously therapy, choice of therapy and method of administration. recorded. In the pre treated group 72.1, 83.4 and 97.2 % of the patients 062-LIT attained euthyroid state at 3, 6, 12 months respectively. Five Bone Pain Palliation with Strontium-89 in Cancer Patients patients needed a second dose after 3 months. No side effect or With Bone Metastases complications were observed. In group B 77.7, 88.8 and 94.4 % of S.Tiskevicius¹, Z.Baranauskas², A.Burneckis², E.Aleknavicius² patients achieved euthyroid status at 3, 6 and 12 months ¹Vilnius University Institute of Oncology, Nuclear Medicine respectively. There was no side effects or complications noted. Department and ²Vilnius University Institute of Oncology, However, 16.7 and 22.2 % of the patients in group A and 27.7 and Oncoradiotherapy Department, Lithuania 36.1 % of the group B became hypothyroid at 6 and 12 months Eighty two patients with painful skeletal metastases of malignant respectively. They were treated with Thyroxine supplementation. diseases (predominantly prostate) were treated with strontium-89 Overall there was no significant difference in the outcome of the in Oncoradiotherapy department of Vilnius University Institute of therapy in both groups (p >0.05). Oncology during 2000-2004 period. The patients received We concluded that it is not necessary to bring hyperthyroid strontium-89 chloride (Metastron, Amersham Health) at a dose of patients to euthyroid state with anti thyroid drugs before 150 MBq intravenously. Pain palliation was evaluated on the basis administering radio iodine. Radio iodine can be considered as a of increase in the Karnofsky performance status, the pain and definitive, effective and safe initial therapy in hyperthyroidism. narcotic test improvement at 3 months. The efficacy of strontium- Only in sever cases of thyrotoxicosis pre treatment may be 89 treatment was graded as good, partial or absent. necessary before subjecting to radio iodine application. The response was good in 52 (63%), partial in 20 (24%), and there was no response in the remaining 10 (12%) of cases. A complete improvement was observed in 13 (16%) patients. Duration of the 064-MON response ranged from 2 to 7 months (mean 3 months). During a 3- Iodine-131 Therapy for the Treatment of Hyperthyroidism year study, strontium-89 treatment was successively repeated up Enkhtuya B, Tsevelmaa L, Erdenechimeg S to 4 times in some patients who benefited from the first strontium- Department of Nuclear Medicine, First State Central Hospital of 89 administration and did not show signs of myelosuppression. National Medical University, Mongolia After repeated treatment, relief was consistent and the effectiveness was as good as after the first dose of strontium-89. Since 1997, radioactive iodine (I-131) has become the most During the course of strontium-89 treatments, transient signs of widely used therapy for patients with hyperthyroidism cased by myelosuppression were observed , with a partial or full recovery Graves' disease in the Mongolia. Our seven years clinical within 5 months. experience was reviewed to evaluate the efficacy of the therapy. In conclusion, palliative treatment with strontium-89 improves the quality of life in most patients suffering from painful skeletal We treated 150 patients (119 female and 31 male) with metastases. If necessary, the treatment may be repeated safely and hyperthyroidism with I-131 (mean dose 8.2 mCi) between 1997 with the same efficacy as is achieved after the first dose. and 2004. The dose calculation was based on 24 hours thyroid uptake, thyroid galnd size and degree of toxicity. We determined 063-MAL their thyroid status after 1 year in relation to age, pretreatment with Role of Antithyroid Drug Treatment Prior to Radioiodine an antithyroid drug, pretreatment thyroid size and whether or not Therapy in Hyperthyroidism there are thyroid nodules. Das BK*, Pradhan PK, Senthilnathan MS, Malhotra G Out of the 150 patients, 87(58%) were euthyroid, 30 (20%) Sanjay Gandhi Postgraduate Institute of Medical Sciences, hypothyroid at 1 year after treatment, and 33 patients (22%) had Lucknow, INDIA (* Presently Visiting Professor, Universiti persistent hyperthyroidism and required second treatment. The Sains Malaysia) patients who had persistent hyperthyroidism were younger in age, had larger thyroid glands, some of them had thyroid nodules and Radio Iodine (RI) therapy is preceded by anti thyroid drug 27 patients (81%) pretreatment with anti-thyriod drugs for more treatment in most centres. There is a general notion that this is a pre than 6 months. requisite for RI therapy. There have been some sporadic reports in Our results showed that the majority of patients with Graves' the past emphasizing that euthyroid state is not necessary in all hyperthyroidism had a effective treatment. However, 22% of cases before RI. However, no prospective randomized study has patients with younger age, larger thyroid glands, patients with been reported in recent literature. The aim of this prospective thyroid nodules and who had anti-thyroid drugs for more than 6 study was to find out whether prior treatment with anti thyroid months had undergone repeated treatment. A higther dose of I-131 drugs showed any advantage in comparison to direct application maybe advisible in such patients. In order to establish correct of radio iodine in hyperthyroid patients. treatment dose we may need more precise dosimetry study. Seventy-two clinically and bio chemically proven cases of hyperthyroidism were randomized into two groups , each with 36 065-MON patients. They were matched by age, sex and size of goiter. After Treatment of HCC with Re-188 lipiodol Initial Experience in establishment of the diagnosis the patients were either subjected to Mongolia anti thyroid drug treatment (Group A) or given calculated dose of Erdenechimeg S1, Onkhuudai P1, Gonchigsuren D2, Sundram FX3, radio iodine (Group B). After being euthyroid for at least 4 weeks Divgi C4, Padhy A.K5 the Group A patients were asked to stop the drugs (Neomercazole) 1 Department of Nuclear Medicine; 2 Department of Radiology, for 3-5 days and radio iodine was administered. Patients in both First State Central Hospital of National Medical University, World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 48. S-42 Abstracts: ICRT-2005 Mongolia; 3 Department of Nuclear Medicine, Singapore General changes histological examination was done in two rabbits. The Hospital, Singapore; 4 MSKCC, New York, USA and 5Gujarat synovial membrane showed round cell infiltrates with Cancer & Research Institute, Ahmedabad, India neutrophiles, leukocytes plasmocytes and histocytes. In addition, there is noted capillary hyperemia. Each rabbits received 37 MBq The aim of this study was to assess the safety and efficacy, in of 188Re-tin colloid. The animals were sacrificed at 1 and 4 weeks patients with inoperable hepatocellular carcinoma (IHCC) of after injection and knee joints dissected and sectioned for intra-arterial 188Re-lipiodol given at an amount of radioactivity histological study. Within one week after injection of 188Re-tin calculated to deliver acceptable radiation absorbed doses to colloid into the knee joints, the synovial membrane showed round critical normal organs (liver, lung and bone marrow). cell infiltrates consisting of lymphocytes, histocytes, fibrocytes Rhenium-188 was eluted from a tungsten/rhenium generator and deposits of fibrin. After 4 weeks, the inflammatory changes system from ORNL. Conjugation of 188Re to lipiodol was carried almost disappeared and there was fibrotic changes and out using a HDD kit from Korea. Both were provided through the epithelization of synovial membrane. There was no damage of IAEA. Thirty nine patients with HCC were studied. Patients had articular cartilage in any histological study. We find good acceptable hematopoietic and hepatic parameters at baseline. All hystological response of 188Re-tin colloid radiosynovectomy in patients had measurable disease on CT. A transmission whole inflammatory joint diseases. body scan was carried out on the morning of the study. A “scout” activity 207 ± 57 MBq of 188Re-lipiodol was administered into the 067-NET relevant hepatic arterial tree accessed in the interventional suite, Interventions in 131I-MIBG Treatment of Neuroendocrine and static images were obtained in Nuclear Medicine to provide Tumours quantitative images of the liver (including tumor), lungs and Hoefnagel CA, The Netherlands Cancer Institute, Amsterdam whole body. The maximum tolerated activity (MTA) was defined as that which would deliver no more than 30 Gy to liver, 12 Gy to Specific targeting of neuroendocrine tumours for therapy may be lungs or 1.5 Gy to red marrow, calculated using a MIRD-based achieved either via the metabolic route (MIBG), via receptor spreadsheet developed at MSKCC, New York, USA. An amount binding (peptides) or via the immunological route (antibodies). of 188Re-lipiodol not more than the MTA was then administered Any malignant neural crest tumour, showing sufficient uptake and under identical conditions. Patients were followed for toxicity retention of 131I-meta-iodobenzylguanidine (MIBG) on a and efficacy until death or disease progression. Twenty one diagnostic tracer study is a candidate for therapy using this agent. patients were treated twice, and two patient three times. The principle indications for 131I-MIBG therapy are malignant The therapy was well tolerated with no major side-effects pheochromocytoma and paraganglioma, neuroblastoma stage III observed. Logistic and other constraints prevented delivery of the and IV, medullary thyroid carcinoma and symptomatic, metastatic MTA in all patients, with 35.5% (1.33-2.7GBq) of MTA being carcinoid tumors. administered. Despite this, 16.6% had major (PR+CR) response At an EANM Radionuclide Therapy Committee workshop on 131I- and 56.6% had stabilization of disease. Quality of life was MIBG therapy in 1999 the results of treatment in 534 patients with improved in 12/39 patients, with a median overall survival of 14 neural crest tumours were gathered, showing cumulative (4-24) months and a median progression-free survival of 9 objective response rates of 51% for malignant pheochro- months. mocytoma, 48% for paraganglioma, 51% for neuroblastoma, 23% We conclude that intra-arterial therapy with 188Re-lipiodol is for medullary thyroid carcinoma and 8% for carcinoid tumors. feasible in Mongolia. The therapy is safe and preliminary efficacy Moreover, symptomatic palliation occurred in more than 60% of results are encouraging. The inability to treat at MTA suggests the patients. These results compare favorably with the best that other methods, including multiple treatments cumulatively reported results of combination chemotherapy. less than MTA, may be considered. The study is ongoing, as is An active uptake-1 mechanism at the cell membrane and analysis of tumor radiation absorbed dose and treatment efficacy. neurosecretory storage granules in the cytoplasm of neural crest tumours are responsible for the uptake and retention of 131I-MIBG, 066-MON respectively, resulting in high tumour/nontumour ratio's. Many Radiation Synovectomy With 188re-tin Colloid in Histological drugs are known or may be expected to interfere with (i.e. have a Study negatively effect on) the uptake and/or retention of 131I-MIBG by Erdenechimeg S1, Tsevelmaa L1, Bayarmaa B2 the tumour cell. In contrast, there are also factors which may 1 Department of Nuclear Medicine of First State Central Hospital, influence either the uptake/retention of 131I-MIBG or the results of Mongolia and 2Department of Pathology, Health Science Medical therapy in a positive way. University, Mongolia Possible interventions: 1. Use of other labels, for example 125I-MIBG, 211At-MABG and 76 Radiation Synovectomy has been widely used treatment modality Br-MBBG, which, in view of their ultrashort pathway, may have of chronic inflammatory joint diseases in many countries. 188Re-tin a role in the treatment of micrometastases and bone marrow colloid is a relatively new radiopharmaceutical agent, which in?ltration, particularly as the results of 131I-MIBG therapy under efficacy and safety were reported and it appears feasible to use in these circumstances are poor. Mongolia. The aim of our study is to generate antigen-induced 2. By increasing the specific activity and the production of non- arthritis model in the rabbits knee, conduct radiation synovectomy carrier-added 131I-MIBG tumour uptake may be improved, with 188Re-tin colloid and demonstrate treatment efficacy by although. the optimal speci?c activity may vary with the tumour histological changes. Six male white rabbits (2-2.5 kg) were used type. in this study. To produce antigen-induced arthritis model 0.5 ml of 3. Prolonging retention, e.g. by calcium channel antagonists. Freund's complete adjuvant was administered twice within two Blake et al. showed that Nifedipine (Adalat) altered the kinetics of 131 weeks by intra-articular injection. To complete inflammatory I-MIBG therapy in some patients: the observed increased uptake World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 49. S-43 Abstracts: ICRT-2005 and retention led to a higher absorbed radiation dose to the tumour. Department of Medical Sciences, PIEAS & Isotope Production 4. Alternative routes of administration may enhance the tumour Division, PINSTECH, Islamabad, Pakistan uptake, for instance via the intra-arterial or intraperitoneal route. When the metastases of a neural crest tumour are confined to the In a quest for more effective radiopharmaceutical for palliation of liver, administration of 131I-MIBG therapy via hepatic arterial pain experienced by metastatic cancer patients, this study relates catheter is feasible. the results obtained with therapeutic beta emitter radionuclides of 5. Combination with other treatment modalities, e.g. Samarium-153, Holmium-166, Yttrium-90 and Lutetium-177 chemotherapy and/or total body irradiation, myeloablative complexed to bone seeking phosphonate ligand of chemotherapy requiring autologous bone marrow or stem-cell ethylenediamine tetramethylene phosphonic acid (EDTMP). The rescue, accepting additional toxicity. In neuroblastoma 131I-MIBG objective of this study is to formulate and evaluate Samarium-153, therapy has been combined with oxygen treatment under Holmium-166, Yttrium-90 and Lutetium-177 labeled EDTMP for hyperbaric conditions and high doses vitamine C, resulting in the bone pain palliation and to compare them with 153Sm-EDTMP that formation of hydroxyl radicals, which are toxic to the is currently being used in many centers of the world. All the neuroblastoma cell on top of the 131I-MIBG radiation effect to radionuclides were prepared by n,ã reaction. Quality control was which it is exposed. checked by paper chromatography and paper electrophoresis. 6. Changing the order of treatments: 131I-MIBG therapy as the Various parameters were optimized to formulate these initial therapy instead of preoperative combination chemotherapy radiopharmaceuticals with maximum labeling efficiency. in children presenting with advanced disease/inoperable Sprague-Dawley male rats were used for biodistribution and neuroblastoma. Initial results have demonstrated the feasibility imaging study. The labeling efficiency of 153Sm-EDTMP was and effectiveness of upfront 131I-MIBG therapy: a higher objective found to be > 99% at pH 7.5 with 1:5 (Sm: EDTMP) molar ratio response rate (>70%) and considerably less toxicity compared to incubated for 20 minutes at room temperature. For 90Y-EDTMP 131 I-MIBG therapy after conventional treatment. the labeling efficiency was > 95 at pH 7.5 with ligand: molar ratio 7. Prevention of tumour cell repair: in high risk neuroblastoma from 5-12. 166Ho-EDTMP showed that the complex can be (stage IV, >1 year of age), upfront 131I-MIBG therapy has been prepared with radiochemical purity of >95% using ligand: molar combined with Topotecan, a topoisomerase I inhibitor, which may ratio from 8-12 at pH 7.5. 177Lu-EDTMP complex showed labeling enhance the radiation induced cytotoxicity by interfering with efficiency >95% using ligand: molar ratio from 20-30 at pH 7.5. repair of damaged cells. During bio-distribution study, skeletal uptake was found to be 8. Combining radionuclide targeting mechanisms: as in nude mice maximum for 177Lu-EDTMP (70±2.4%), followed by 153Sm- with SK-N-SH neuroblastoma xenografts the therapeutic efficacy EDTMP (58.5±2.8%), 90Y-EDTMP (45±2.1%) and 166Ho-EDTMP of 131I-labelled anti-L1-CAM antibody chCE7 in comparison with (36±2.1%). All these radiopharmaceuticals showed good renal 131 I-MIBG and in patients the complementarity of these agents in and rapid blood clearance. The biodistribution study of free targeting neuroblastoma was demonstrated, combined or radionuclides showed significant uptake of activity by soft tissues alternating MIBG- and radioimmunotherapy may be a future including lungs, liver and spleen, with minimal uptake in the approach. skeletal system (153SmCl3: 7.5±0.04%, 90YCl3: 1.75±0.6%, 166 9. Induction of tumour cell differentiation, e.g. using retinoic acid HoCl3: 3.3±0.3%, 177LuCl3: 2.5±0.1%). Imaging study carried or interferon, may increase the speci?c uptake and retention of out for 153Sm-EDTMP, 177Lu-EDTMP and 166Ho-EDTMP showed 131 I-MIBG in tumours. The successful transfection of the good uptake of activity by the skeletal system (including noradrenalin transporter gene (NAT) into NAT negative epiphyses, spine and facial bones). neuroblastoma cell lines offers another possibility to improve the Therefore, it was concluded that labeled complexes of these efficacy of MIBG therapy. lanthides can be used effectively in the therapy for bone pain 10. Blocking extratumoural specific uptake by unlabelled (“cold”) palliation, 177Lu-EDTMP have more potential in this regard. MIBG. In nude mice with PC-12 pheochromocytoma xenografts Chlorides of the lanthides cannot be used for bone pain palliation excess unlabelled MIBG leads to significant reduction of tumour due to their poor skeletal localization. uptake of 125I-MIBG, but in patients with carcinoid tumors treated with unlabelled MIBG favourable changes in the biodistribution 069-PAK of 131I-MIBG were observed, increasing the tumour/non-tumour Trans-Arterial Radioconjugate Radionuclide Therapy For ratio by a factor 1.1-2.1 in 70% of the patients. Combined therapy Hepatocellular Carcinoma; Feasibility & Applications In of high dose unlabelled MIBG followed by 7.4 GBq 131I-MIBG Pakistan may result in a greater biochemical response and palliative effect Asghar S than each of the treatments alone. INMOL, Lahore, Pakistan I conclude that 131I-MIBG therapy is effective in several neural crest tumours, attaining 50% objective response in Abstract not received pheochromocytoma, paraganglioma and neuroblastoma and providing excellent palliation to most patients. The tumour 070-PER targeting and therapy effectiveness may be enhanced by Impact of Educational Strategies in Positioning Samarium- pharmacological interventions and by combination with other 153 EDTMP as a Treatment for Metastatic Bone Pain treatment modalities. Seminario C, Morales R, Castro M, Cano RA, Mendoza G Center of Nuclear Medicine (Instituto Peruano de Energía 068-PAK Nuclear) IPEN-INEN Formulation and evaluation of Beta-emitting Radionuclide Labeled EDTMP for Bone Pain Palliation To educate is a difficult task but its results make efforts Sohaib M, Mushtaq A, Jehangir M, Yousuf M, Azra P worthwhile. Many patients in Peru suffer from intractable bone World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 50. S-44 Abstracts: ICRT-2005 pain due to metastases. Since 1993 radionuclides were used to 071-PER palliate bone pain due to metastases in Peru. First, with the help of Influence of T-3 produced by Metastatic Thyroid tissue on the IAEA, Peru participated in a clinical trial using Phosphorus 32 Iodine-131 Treatment Outcome and Strontium 89. Then, efforts were performed to produce Mendoza G1, Cano RA1, Morales R1, Martínez F1, Saavedra P1, Samarium 153 EDMTP locally, which was achieved in 1995. Vílchez C1, Postigo J2, Sánchez P2, Salas A2, Torres F2 Nevertheless, years passed and Samarium use did not increase 1 Center of Nuclear Medicine (Instituto Peruano de Energía proportionally to the needs of people with cancer and bone pain, Nuclear) IPEN-INEN and 2Head and 2Neck Cancer Department, mainly the poor. Educational strategies have been proven useful Instituto Especializado de Enfermedades Neoplásicas (INEN) for delivering solutions to many health problems in other diseases and also in cancer. Health education makes patients and their Iodine 131 is currently used as adjuvant therapy for patients with relatives assume responsible care of their problems. The purpose differentiated thyroid cancer since 1960, although influence of of this work was to increase Samarium EDTMP use as palliative this treatment on survival of some patients remains controversial. treatment in patients with bone pain due to metastases, using Different approaches have been taken to select which patients will educational strategies as means to change attitudes towards this really benefit from iodine 131 treatment. There are some reports health problem. stating that TSH stimulation is not vital to select patients for In September 2003, a task group conducted studies in order to ablation or treatment with iodine 131. The objective of this study apply several methods to achieve the goal of increasing Samarium is to determine if the production of T3 by metastatic thyroid tissue EDTMP use. Educational strategies employed were performed to has any influence on iodine 131 treatment outcome. provide verbal and written information to patients, physicians, Nineteen patients with differentiated thyroid cancer who had been medical students, residents, pain specialists, oncologists and treated with total thyroidectomy and had received at least one dose neurologists, as well as general public. Verbal information of ablative treatment with iodine 131 were studied. Hormone included radio interviews, television spots and a phone number (in replacement treatment with T4 was withdrawn in these patients, charge of two secretaries, prepared for answering and if not for one month. All patients had a whole body scan after iodine 131 possible, a physician was in charge of attending patient therapy. TSH, fT4 and T3 were determined by RIA after consultation), email and a web page for consultation. Written withdrawal of treatment with T4. Patients were divided in two material was delivered to several newspapers, including clinical groups: One group had T3 < 60 ng/100 ml and the other one, T3 > use of Samarium, possibilities of being elected for treatment, 60 ng/ml. Tg was measured in both groups before and after benefits and risks and a photography of the product. Politics of the treatment with iodine 131. A positive outcome was defined when institution producing Samarium changed, in order to achieve Tg < 5 ng/ml and/or a negative whole body scan. Persistent minimum cost of the product and it was delivered to all publics at disease was considered if Tg was > 5 ng/ml, had no change or the lowest cost for a year, which has finished in December 2004. increased, or if the whole body scan remained positive. Thirteen Three television spots were delivered to public: “Hello, Doctor”, patients had T3 < 60 ng/100 ml (median = 35,0 ng/100ml, range = which has a morning audience and in two interviews in news 11,3-57,5) and six had T3 > 60ng/100ml (median = 82,9 ng/100 programs, with high rating performance. Five interviews were ml, range = 65,6-132,0 ). Outcome after further treatment with given in radio programs, one of them was for a feminine audience, iodine 131 in both groups is shown in Table 1. three for general public and the other two with national impact. In T3 Response to No response Total every program a web page, an email and a telephone number were (ng/100 ml) treatment Tg > 5 ng/ml Tg < 5 ng/ml given for consultation. In Nuclear Medicine Centers in Lima telephone calls have been received since the beginning of the < 60 5 8 13 campaign every day, up to date. In a year, a monthly conference > 60 1 5 6 Total 6 13 19 Table 1 Influence of T-3 produced by Metastatic Thyroid tissue on Iodine-131 Treatment Outcome Considering necessary to select patients for improving outcome of treatment with iodine 131 in thyroid cancer patients, the results of the present investigation show that there is a tendency towards non responsiveness in patients producing T3 in metastatic thyroid tissue. Further studies with a greater number of patients and longer follow-up are necessary to arrive to some conclusions and possible management of these cases. 072-PHI Figure 1 Sale of Samarium increased as a result of end-user awareness Therapeutic Options in the Management of Autonomously was delivered to physicians. Samarium EDTMP treatment Functioning Thyroid Adenomas increased substantially after the campaign (Figure1) Barrenechea EA, Ong A The more significant means in mass media for changing Veterans Memorial Medical Center and St Lukes Medical Center, management were patient education, continuous meetings with Manila, Philippines specialists and one of the television spots used (“Hello, doctor”), which continues to be delivered in the closed circuit TV network Autonomously functioning thyroid nodules or adenomas (AFTN of the social security system. or AFTA) was established as a clinical entity in 1918 by Goetsch We conclude that repetitive educational strategies have a positive correlating cellular mitochondrial content with nodular function impact in delivering radiopharmaceuticals for bone pain palliation and showing the inverse correlation between AFTN function and to patients with bone metastases extra nodular tissue function. They are almost always benign and World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 51. S-45 Abstracts: ICRT-2005 degeneration, which is common in AFTN, can result in the 073-PHI development of hyperthyroidism. It is therefore important to know The Value of PET in DTC with Negative WBS but with the function of these nodules by requesting for the thyroid function Elevated Thyroglobulin levels tests namely T3, T4, and TSH. They are diagnosed by thyroid Barrenechea EA, Ong A, Santiago J scans using I-131 or Tc 99m as a hot solitary nodule in one lobe Department of Nuclear Medicine, St Lukes Medical Center, with the other lobe not appearing on scan or suppressed. The Quezon City, Philippines frequency of AFTA worldwide is quite variable depending on geography. It ranges from 1% in North America to 10 % in some The ability to detect and treat thyroid cancer early is critically areas in Europe and Asia or in areas of iodine deficiency. The important as most differentiated thyroid cancers (DTC) have very traditional methods of treatment of these nodules have been good prognosis. There are, however certain varieties that are quite surgery and radioactive iodine ablation. Surgical treatment as a aggressive and these are usually the ones with elevated rule is indicated in young patients with nodules larger than 3 cm thyroglobulin but with negative I-131 whole body scans. These and those with local compressive symptoms. RAI is used in DTC usually transform over time and de-differentiate and lose elderly patients and those who are poor surgical risks. The usual some or all of their ability to absorb radioactive iodine. These cells dose ranges from 20 to 30 mCi and is definitely larger that when may, however still be able to absorb FDG (used in PET scan) treating Graves' disease. Others have resorted to PEI or which could suggest thyroid cancer cells. This study was percutaneous ethanol injection with reported success. There has conducted in patients with DTC namely papillary and follicular been no definite management of these AFTA due to the variable with negative whole body scans using I-131 but with elevated natural history and some would only recommend observation for serum thyroglobulin levels of over 10ng/dl. These patients have asymptomatic small adenomas, which are euthyroid. Therefore undergone total thyroidectomy or NTT and I-131 therapy. This this paper studied the results of treatment using RAI ablation, was done to determine the usefulness and value of the FDG PET surgery or plain observation for AFTA. Percutaneous ethanol for thyroid cancer cases. injection is not being done in our center. In the local setting, where There were 15 patients in all, with 11 females and 4 males. Age thyroid disease is still endemic, the incidence of AFTA is not so range was 17 to 78 years old. Fourteen cases had papillary thyroid high. Graves' disease is still the predominating cause of cancer and one had follicular type. Of the 15 patients, eleven (11) hyperthyroidism followed by multinodular goiter. Toxic AFTA had negative whole body scans using 5mCi of I-131 with elevated occurs in 3% of the total hyperthyroid patients. In a ten-year serum thyroglobulin levels ranging from over 10 ng/dl to review of the course of the disease after treatment with any of the 311.12ng/dl .All these patients underwent PET scans and showed three modalities of surgery, RAI and purely observation, there still positive results. The other four patients had faint tracer uptake by seem to be no common consensus, which the best treatment I-131 WBS and showed positive PET results with additional sites modality is. Forty-eight patients were included in the study. of metastases. Among these patients were 43 females and 5 males. Majority were We conclude that FDG PET scan is a sensitive tool to detect over fifty years old. Among the 48 patients, thirty-nine were toxic radioiodine-negative recurrence and metastases in patients with and 9 were non-toxic. Of the toxic patients, twelve patients elevated serum thyroglobulin levels among thyroid cancer underwent surgery of the affected lobe, undergoing lobectomy or patients. The value of PET lies in the fact that it can impact or nodulectomy, while 19 patients were given radioactive iodine with change the treatment and early diagnosis of thyroid cancer can be a dose range of 20 to 30 mCi. Eight patients just had antithyroid made. drugs and were just observed. Among the nine patients who were euthyroid, five were just observed but requiring periodic follow- 074-PHI up while four underwent surgery. Two of the total population, one Comparative Evaluation Of The Efficacy Of hyperthyroid and one euthyroid patient while being observed after Radiosynovectomy With Conventional Intra-articular 6 months and three months respectively developed rapid growth Therapy In Rheumatoid Arthritis And Haemophilic of the nodules. FNAB was done which showed well differentiated Arthropathy (CERAHA) CA (papillary and follicular) hence underwent total Barrenechea EA, Navarra S, Chua, M. thyroidectomy or near total thyroidectomy, RAI ablation and Dept of Nuclear Medicine, St. Lukes Medical Center, Quezon lifetime thyroid hormone suppression. The results of the 3 City, Philippines modalities were compared and the best results were seen in the group given RAI in terms of cost effectiveness, diminished size of The objective of this study is to determine the therapeutic efficacy the nodules to disappearance of nodules and relief of symptoms. of radiosynovectomy on rheumatoid and hemophilic arthropathy Hypothyroidism was not a problem as only two patients as compared to the usual intra-articular steroids on painful joints. developed such. Those who were observed only still had the Rheumatoid arthritis is a chronic, systemic and inflammatory nodules, which became bigger in size with the antithyroids while disease that involves the joints and is quite disabling. It has a the incidence of hypothyroidism secondary to surgery was higher worldwide prevalence of 1%. Hemophilia is a congenital blood in this study as seen in 4 patients. In conclusion, the three modes of disease that produces abnormal bleeding at the musculoskeletal treatment has its own weaknesses and strengths and treatment level. It is a sex-linked trait that cause coagulation defects brought should be individualized depending on which age group the about by lack of Factor Vlll for Hemophilia A and Factor lX for patient belongs (very important consideration) as well as patients Hemophilia B. In this study, under the auspices of IAEA, we used choice, size of the nodule and function of the nodule. I-131 may Yttrium 90 colloids and Rhenium 188 intra-articularly in the knee still be the treatment of choice especially in the elderly since they in the experimental group and steroids on the control group. have concomitant cardiac problems. However in the younger age Radioactive colloids (beta radiation) create fibrosis of the group and for bigger nodules, surgery may be preferred for hypertrophic and highly vascularized synovium. It leads to aesthetic reasons and since they are good surgical risks. Pure coagulation necrosis and sloughing of the cells, destroying antithyroid treatment usually is not recommended. diseased pannus and inflamed synovium with the hope that the World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 52. S-46 Abstracts: ICRT-2005 regenerating synovium, after destruction, will be free of the diagnosis of papillary, follicular or mixed type of thyroid cancer. disease. Included in this study were established cases of RA set by They all have undergone near total thyroidectomy or total the American Rheumatoid Assn which are stage 1, 2, and 3 by thyroidectomy and without any evidence of metastatic disease. Larsen classification, no ankylosis, non-responders for NSAIDS Four to six weeks after the surgery and without thyroid hormone and DMARDS for at least 6 months and with their informed maintenance as well as iodine free diet and drugs, they underwent consent. For the hemophilic group, they should have at least 3 a total body scan and uptake using 1-3 mci of I-131. Serum TSH bleeding episodes for the last six months and at least with 30% and thyroglobulin were also taken. Randomization was made thru coagulopathy at the time of the procedure. Exclusion criteria the IAEA and the patients either got a low dose or a high dose included being pregnant or lactating, with infection on site of depending on such randomization. Of the 86 patients included, injection, beyond stage 3 and presence Baker's cyst. Baseline there were a total of 76 evaluable cases. There were three dropouts radiography and two-phase bone scans were taken as well as because of other medical conditions as upper GI bleeding, lung repeating these procedures at 6 an 12 months post-treatment. cancer and leg fracture. The 7 other patients have not completed There were 39 evaluable patients under the experimental group their follow-up body scan. Among these patients were 67 females consisting of 18 RA patients (mostly females) and 21 HA patients and 19 males whose age range was 19 to 84 years old. There were (all males). Thirty-eight patients were given Yttrium-90 colloid 65 cases with histologic type of papillary cancer, 15 follicular and with doses ranging from 60 Mbq to 185 Mbq depending on the age 6 mixed varieties. Forty-one patients were randomized to the high of the patients and one patient was given Rhenium 188 colloid. dose group while 35 patients were assigned to the low dose Fifteen patients were included in the control group where therapy group. These patients were confined till their radiation intraarticular Triamcinolone was given at 10 mgs dose. The results activity was below 2mR/hr. Monitoring of the patients were done of this study is very encouraging with regards the experimental during their hospital stay. Post-therapy body scan was done but not group. Clinical improvement was very evident in most of the with all patients. Most of the side effects noted were sialitis, mild cases. These are based on the pain scoring system based on the neck pains, nausea and occasional vomiting as well as ageusia. visual analog scale, lesser requirement for drugs, diminution of These patients were maintained on thyroid hormone depending on swelling, ability to ambulate, better quality of life, deformity and their sensitivity but almost all were given 200-300mgs per day. lesser episodes of bleeding and hence lesser or no need for Factor The older patients tolerated only around 150mcgs/day. After four VIII transfusion. In most of the hemophiliacs there were no more to six months, serum TSH, thyroglobulin and total body scan were episodes of bleeding, and marked improvement on bone scans. repeated. Successful ablation means there are no residual tissues Pain at baseline was more common for the RA patients. in the neck or an uptake of less than 0.2% as well as a low Improvement was most evident in the hemophilic group thyroglobulin of at least less than ten. consisting of no further bleeding episodes especially after a month Dose Failure Successful ablation P-Value of the therapy and if there were any episodes of bleeding, most Low dose (50mCi) 48.6% (17/35) 51.4% (18/35) 1.000 Not Significant hemophiliacs did not require Factor VIII replacement. Their High dose (100mCi) 36% (15/41) 63.4% (26/41) 0.027 Significant quality of life also improved having fewer absences in school and work. Of course objective findings as x-ray and bone scan also Success rate of ablation in low dose vs. high dose of I-131 showed marked improvement in the HA group while in the RA The success rate for ablating residual thyroid remnants in the neck group some patients (2) remain unchanged on repeat scintigraphy. is more evident in the high dose group (100mCi), p= 0.027 as For the RA group, there was also marked improvement but it was compared to the low dose (50mCi) group, also dependent of the stage when they got into the study. Those on p= 1.000. All patient characteristics were not significantly Larsen Stage 1 and 2 responded quite well while those with different from the two randomized groups. Factors affecting beginning on Larsen 3 scores responded partially. In the control success or failure of ablation could be the size of the residual group under steroids, most of the patients had immediate thyroid tissues to be ablated, the degree of hypothyroidism during improvement but the pain relief and swelling only lasted for one to the therapy as well as the patients' inherent sensitivity to the two months wherein by this time the DMARDS and oral steroids treatment. and NSAIDS take over. Side effects noted after the procedure were initial flare in 4 cases, fever in 2 patients, and a minor skin 076-PHI discoloration in one patient. In conclusion, radiosynovectomy is a Incremental Value of Nitrate Enhancement in Tc-99m minor intervention, cost-effective and can be done on an Sestamibi Myocardial Perfusion Imaging With Spect In outpatient basis. It is effective in those refractory to medical Patients with Coronary Artery Disease and Previous therapy and those not suited for surgery as in haemophilics. Myocardial Infarction Duldulao MA, Obaldo J 075-PHI Nuclear Medicine Section, Philippine Heart Center, Quezon City, Prospective Randomized Trial for the Evaluation of the Philippines Efficacy of Low Vs. High Dose I-131 for Post Operative Remnant Ablation in Differentiated Thyroid Cancer Administration of nitroglycerine before Tc-99m sestamibi Barrenechea EA, Laureta EG, Gaston JC, Al-Nahhas A, Padhy AK imaging improves tracer uptake in resting hypoperfused regions. Nuclear Medicine Dept., Veterans Memorial Medical Center and The aim of this study was to assess the role of NTG in Tc-99m St Lukes Medical Center, Quezon City, Philippines sestamibi myocardial perfusion imaging of patients with coronary artery disease and previous myocardial infarction and whether it The study was done under the auspices of the IAEA to evaluate the still has a role in cases of severely hypoperfused myocardium. All efficacy of low dose (50-60mCi) vs. High dose (100 mCi) for the the thirty five who underwent two Tc-99m sestamibi myocardial post-operative remnant ablation of differentiated thyroid cancer perfusion imaging with SPECT, one at baseline and the other after and to determine other factors associated with successful ablation. NTG administration (0.6 mg sublingual) at least 24 hours apart There were eighty-six patients included in the study with a were included in this study. All have previous history of World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 53. S-47 Abstracts: ICRT-2005 myocardial infarction and angiographically proven CAD or CAD of 131-I were calculated on the basis of iodine uptake, goitre size suspect. Seven out of the total thirty five patients have rest/stress and an assumed absorbed dose. Marinnneli's formula was applied. imaging. Qualitative segmental analysis and perfusion scores of The assumed absorbed doses were diversified according to the each segment were assigned. There was significant reduction of cause of hyperthyroidism and the size of goitre, and ranged from perfusion scores in nitrate-augmented Tc-99m sestamibi 80 to 350 Gy. In case of small goitres the absorbed doses varied compared to baseline (from 30.1 ± 12 to 26.6 ± 11, p<0.0001). from 80 to 100 Gy. In case of Graves' disease - from 80 to 150 Gy, The degree of severity at rest was also related to the effect of in solitary nodules from 200 to 350 Gy. 131-I was given to nitrate, i.e. nitrate administration is more beneficial when mild to patients orally in capsules. The administered therapeutic doses moderate defects were seen at baseline study (p<0.002). The ranged from 200 mCi to 800 mCi. Steroid protection was given to overall detection rate of reversible segments with NTG was 44%, patients with Graves' disease and mild opthalmopathy. This observed to be higher in patients without stress-induced ischemia. consisted of administering Prednisone orally from the third day The degree of stress defects was not related to the effect of nitrates, after radioiodine in doses of 0.5mg per kg for four weeks and then therefore, even in the presence of severe to absent tracer uptake on a gradually reduced dosage for the next two months. Follow up stress images, nitrate-enhanced imaging may still be beneficial. examination was performed after 4-6 weeks, then after 2 months, Nitrate augmentation has incremental diagnostic value in Tc-99m 4 months, 6 months and 12 months after radioiodine sestamibi myocardial perfusion imaging in patients with coronary administration. These studies involved a physical examination artery disease and myocardial infarction. It potentially improves and biochemical tests like TSH, fT3 and fT4. detection of severely hypoperfused but viable myocardium. The The study group consisted of 4913 patients, including 4244 routine use of nitrate in myocardial perfusion imaging should be women (84%) and 769 men (16%) were treated in the Nuclear encouraged especially when selecting patients for Medicine Department of the Medical University Hospital of revascularization. Bia³ystok. Hyperthyroidism caused by Graves' disease was discovered in 17% of the patients, including 597 women and 260 077-PHI men. Multifocal autonomy - in 40% of patients: 1712 women and Radionuclide treatment of Liver Cancer using Re-188 256 men, whereas unifocal autonomy in 43%: 1853 women and Lipiodol: Experience in Philippines 253 men. San Luis TOL, Ogbac R, Barrenechea E, Ang S After 12 months of follow-up, radioiodine therapy proved to be St. Lukes Medical Center, 279 E. Rodriguez Blvd., Quezon City successful in 74% of patients. Hypothyroidism was found in 12 %, 1102, Philippines and in 14% subclinical and/or symptomatical hyperthyroidism. The best effects were achieved in the group with unifocal Abstract not received autonomy - euthyroid in 92%, a lower effectiveness in multifocal autonomy euthyroid in 87%, and the least successful therapy - 078-POL 72% - in the group with Graves' disease. Due to persistent A Retrospective Assessment of the Effectiveness of hyperthyroidism, further radioiodine doses were applied in 28 % Radioiodine Treatment of Hyperthyroid Patients from 1997 to of Graves' disease patients, 13% of multifocal autonomy patients 2003 in the North-Eastern Region of Poland. and 8 % of unifocal autonomy patients. In case of patients with Budlewski T, Rogowski F, Szumowski P, Parfieñczyk A, Sopotyk Graves' disease who were given steroid protection, no increase of A, Kociura-Sawicka A, Abdelrazek S opthalmopathy was discovered. The Department of Nuclear Medicine, Medical University Compared to other studies, the presented results of RIT seem to be Hospital, Bia³ystok, Poland highly effective. The high therapeutic effectiveness of this method is the result of a suitable preparation of patients and proper doses The first clinical studies concerning treatment of hyperthyroid calculated with consideration for such factors as the radioiodine patients with 131-I date back as far as 1941. However, it was the uptake, the effective half live of 131-I and the size of the goiter. It following years that brought a wide application of these methods. also results from a specific form of hyperthyroidism in the region: In Podlasie region (north-eastern Poland) radioiodine treatment over 80% of hyperthyroidism is caused by unifocal autonomous was first introduced in 1997. Hyperthyroidism in this region and multinodular hyperthyroid goiter. The long-term results of affects about 1.5% of population. The number of new patients is RIT in this region will be known once an additional analysis is about 3,500 per year. Because iodine deficiency is high in this conducted after a 5 and/or 10 year period. region, toxic nodular goitre rather than Graves' disease tends to be the main cause of hyperthyroidism. The aim of this study was a 079-POL retrospective analysis of the results of radioiodine treatment of Intravascular radionuclide therapy using Re-188 Perrhenate hyperthyroid patients from 1997 to 2003. to prevent re-stenosis following PTCA: Initial Experience in From 1997 to 2003, 4913 hyperthyroid patients underwent Poland treatment with 131-I (131-I Polatom, Œwierk) in the Nuclear Birkenfeld B et al Medicine Department of the Medical University of Bia³ystok. The Department of Nuclear Medicine, Pomerian Medical University, tested group included: 2106 patients with single solitary nodule, U1. Unii Lubelskiej 1 1968 with multinodular goitre and 839 with Graves' disease. The PL-71-252 Szczecin, Poland diagnosis was made on the basis of physical examination and biochemical test results including TSH, fT4 and fT3. All patients Abstract not received had scintigraphic studies with 24 and 48 h uptake of 131-I. They also underwent ultrasound scans to enable assessment of the goitre size and to discover the nodules. All patients with nodules revealed by physical examination and ultrasound scans had biopsy performed under ultrasonographic control. The therapeutic doses World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 54. S-48 Abstracts: ICRT-2005 080-POL ppm, but later on did not exceed 10 ppm. Sentinel Lymph node mapping and detection in patients of To check the suitability of the 188Re eluate for medical purposes, melanoma: Role in prognosis a lyophilized kit preparation of hydroxyethylidenediphosphonate Birkenfeld B et al. (HEDP) for labelling with 188Re has been developed. To prepare Department of Nuclear Medicine, Pomerian Medical University, 188Re-HEDP up to 97 mCi in 2ml eluate of sodium perrhenate U1. Unii Lubelskiej 1 was added to a vial containing 5.0 mg HEDP, 4.9 mg SnCl2, 2.9 PL-71-252 Szczecin, Poland mg ascorbic acid and 0.5 mg KReO4. Then 200 ml of 3 M HCl was added to lower pH to 0.5 1. The whole mixture was heated for 15 Abstract not received min at 95?C to 100?C, allowed to cool, whereafter 2.0 ml sodium acetate solution (39mg/ml) containing 50 ml 30% NaOH was 081-POL added to adjust the pH to 5-6. The radiochemical purity was 188W/188Re generator as a convenient source of 188Re determined by ITLC-SG using 0.9% NaCl as solvent and paper perrhenate solution and a kit for preparation of 188Re- chromatography using Whatman 1 and acetone as developing HDEHP solution. Using saline as eluent, 188Re-HEDP and perrhenate Mikolajczak R1, Korsak A1, Zuchlinska M1, Pawlak D1, Konior M2, move with the solvent front and only reduced colloids or ReO2 Zelek Z2 remain at the origin, while using acetone, 188Re-HEDP stays at 1Radioisotope Centre POLATOM, 2POLATOM Sp. z o.o., the origin and free perrhenate moves with the solvent front. Swierk-Otwock, Poland Stability of 188Re-HEDP was observed when stored at 20-25?C for 1, 2, 3, 24, and 48h. Radiochemical analysis indicated high From the number of beta-emitting radionuclides useful in internal yields of labelling above 99% when stored at 20-25?C for 24 h, radiotherapy several can be produced at the Radioisotope Centre and the labelled compound being stable for 48 h (RCP>96%). POLATOM either in a carrier-added (153Sm, 166Ho, 186Re) or in We also analysed 188Re-HEDP biodistribution and bone uptake a carrier-free form (90Y, 177Lu), based on the locally developed following intravenous injection in Wistar rats to assess its technologies. Recently our efforts were focused on the potential for clinical use. It showed that the radioactivity in the development of 188W/188Re generator which would provide bone tissue was as high as 2.68% ID/g at 1 h increasing to 3.32% pharmaceutical grade 188Re. In this paper we present our ID/g at 3h. The activity level in the kidney was the highest at 1 h experience with the preparation of a portable 188W/188Re (0.79% ID/g) but then decreased through the study. Radioactivity generator and its stability over the period of several months. The in the blood, lung, liver, spleen, and muscle was low (0.23% ID/g eluate of 188Re perrhenate obtained from this generator has been the highest of each of these organs) at 1 h and cleared out rapidly. successfully utilized to produce 188Re-HDEP, a therapeutic agent The bone/muscle ratio was 26.8 at 1 h and increased to 55.7 at 24 h. useful in palliative treatment of painful bone metastasis. The results of this study showed that using standard alumina The rhenium-188 (T1/2 = 16,9 h) is a beta-gamma emitting column it is possible to produce stable 188W/188Re generator radionuclide (Eâmax=2.12 MeV) suitable for therapeutic providing 188Re eluate suitable for medical purposes. The application while its gamma emission (155keV) allows evaluation preparation 188Re-HEDP is sufficiently stable, high level of of biodistribution of radiopharmaceuticals and radiation deposition in bone was observed while injected intravenously to dosimetry studies. Radionuclide 188Re is produced in decay of healthy rats. The kit formula for preparation 188Re-HEDP 188W, which in turn is obtained by neutron activation of 186W in a provided an alternative promising radiopharmaceutical to treat high flux nuclear reactor according to the following and diagnose bone metastases. reaction:186W (n,g) ® 187W (n,g) ® 188W. For preparation of the generator high specific activity 188W 082-POR (RIAR, Russia) as well as the alumina column and the shielding Therapeutic Radiopharmaceuticals (Radioisotope Centre POLATOM, Poland) used for M. Neves. A. Kling and A. Oliveira manufacturing of 99Mo/99mTc generators were used. The Instituto Tecnológico e Nuclear, Estrada Nacional no.10, 2686- generator column containing alumina was activated using 0,9% 953 Sacavém, Portugal NaCl solution (pH = 3.0). Then the 5,5 GBq of 188W (195 GBq/g W) in the form of tungstenic acid was slowly loaded on the column The clinical use of radiations was envisaged soon after the (flow 0,1 ml/min). After 188W deposition the alumina column discovery of X-ray by Wilhelm C. Röntgen in 1895. During was washed with 0,9% NaCl solution (pH = 5.0 6.0). The decades, radiations were used on an empirical basis lacking rigor generator was eluted 2-3 times per week over the period of 6 in dosimetry and radiation protection. These difficulties have been months. The generator yield was calculated as 188Re activity surpassed as the scientific knowledge and technology obtained versus theoretical one. The radionuclidic purity of the progressively developed. Energy from radiation may be delivered eluates related to the 188Re activity was checked by g- externally or internally. In the later case, solid implants into or next spectroscopy. The radiochemical purity of eluted 188Re- to the targeted tissues are used for a short period of time or on a perrhenate solution was determined by TLC method and its long term (brachytherapy). Radiotherapy planning is of chemical purity assessed by ICP-Optical Emission spectrometer primordial importance, because it is necessary to ensure that a (Optima 3300 XL, Perkin-Elmer). therapeutic radiation dose is delivered to a defined three- The elution yield of 188Re calculated on the elution time was well dimensional target volume, while effects on the surrounding above 80% of the theoretical activity and more then 90% of eluted healthy tissues are to be minimized. Several models for the activity was collected in first 4 ml of the eluate to give radioactive quantification of biologic radiation response concerning dose, concentrations up to 100mCi/ml . We also observed low level of dose-rate, and number of dose fractions, total irradiation time etc. radionuclidic impurities in eluate (less then 5*10-2 %). The were developed. The most commonly used is the linear quadratic content of 188W (188W break-through) was lower then 2*10-2 (LQ). It is based on sub-cellular biophysical events and combined %. Only in the first elution the Al concentration was about 200 with clinical experience in order to provide a guideline for external World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 55. S-49 Abstracts: ICRT-2005 radiation therapy and brachytherapy in the form of a therapeutic A large number of potential therapeutic radionuclides that emit index. low energy (conversion and Auger), intermediate and high energy Internal radiotherapy with radiopharmaceuticals Targeted electrons (- emitters), and -particles are known. In general, TR of Radiotherapy (TR) - has so far played a relatively small role in small targets like single cells or small clusters of cells, require nuclear medicine practice. It was restricted to the use of iodine- short-range high-LET radiation as -particles or Auger electrons 131, developed more than 50 years ago for the treatment of thyroid emitters with energies below 40 keV. As the radiobiological cancer. In the past few years, TR has seen a rapid growth as a response depends on the location at which the decay is taking consequence of improvements in tissue specific biomolecules, place and as radiopharmaceuticals are never deposited to 100% on and its potential advantages over external and solid implants. In the targeted organ or tissue, the choice between of - and --emitters particular, for patients with inoperable or multi-site disease it is an should be done criteriously. The use of positron emitting effective complement or alternative to chemotherapy. Since TR radionuclides such as Cu-64, In-114m, I-123, Tb-149, Hg-195m requires the administration of significantly higher activities than etc. for TR is questionable since the interaction of positrons in in diagnostic applications a larger number of exigencies are tissues results in the 511 keV annihilation photons. These necessary: high target binding, uniform target distribution, constitute a major contribution to the absorbed dose in the minimum irradiation of critical organs, effective biologic dose surrounding healthy tissues. Nevertheless, positron emitters may response, precise estimation of radiation dosimetry, radiation be valuable for the selection of radioimmunotherapy candidates protection safety, etc. Therefore, substantial efforts in several by confirming tumour targeting and/or estimating radiation doses. research areas as: radionuclide production, radiopharmaceutical Since the biodistribution and pharmacokinetic differ according to chemistry, medical physics and radiation biology, etc are required. the labelled molecule, dosimetry is much more complex. TR is a TR is based on the selective deposition of cytotoxic ionizing form of continuous radiation delivery, during which the dose rate radiation from the radionuclides attached to the specific is not constant but rises quickly from zero to a maximum value and biomolecules that damages or destroys cells. Since differences in then slowly decreases to zero. The linear-quadratic radiosensitivity among tumour cell types can decide on the radiobiological model may be applied for TR optimisation to success or failure of targeted radiotherapy, the following select a near-optimal radionuclide in terms of an appropriate additional aspects have to be considered: i) The appropriate biological response. The radiobiological processes and the LQ radiation absorbed dose (which should match the biologic formalism are essentially the same for all radiotherapy forms, but desirable effect), and consequently the properties of the in the case of TR dose-limiting values are imposed by the radionuclide emissions (type of radiation, energy and half-life); irradiation of critical organs. ii) The biological response, i.e. the response of cells to radiation as A list of 64 radionuclides, including 20 new potential candidates radio- sensitivity, repair capacity and proliferation rate or for TR is presented in terms of the suitability of their energies for repopulation; iii) The continuous refinement of nano and killing tumour cells which grow as single, small, intermediate and microdosimetry in order to increase the accuracy and the large clusters. The new 20 potential radionuclides can also be dose/response correlations. considered appropriate for intracavitary, intratumoral or In conventional radiotherapy, the terms low, medium and high permanent implants. dose rates are still common, but in TR these terms have no more specific meaning since it is possible to exploit subtle differences in 083-ROM the radiation doses provided by a wide range of radionuclides. The Radioiodine therapy of differentiated thyroid cancer in role of a radionuclide is to deliver a cytotoxic absorbed dose, patients with negative diagnostic I 131 scintigraphy and high sufficient to overcome the cells response in terms of repair and serum thyroglobulin level proliferation. In addition, only a minimum absorbed dose should Gherghe M, Goldstein A, Dumitriu L. be delivered to the surrounding healthy tissue. The absorbed dose Sf. Ioan Clinical Hospital, Bucharest, Romania and National delivered to the cancer cells by a radionuclide should be Institute of Endocrinology “C.I. Parhon”, Bucharest, Romania intrinsically related to the radiobiology response in terms of the relative ability of different tissues to recover from radiation Serum thyroglobulin (Tg) is an important marker in the follow up damage and the absolute ability to control concurrent tumour re- of differentiated thyroid cancer (DTC) patients. Raised Tg level in growth. As each human cancer has its own cellular cytoxicity and the presence of negative antithyroglobulin antibodies is an cytoprotective response to ionizing radiation a certain energy indicator of persistent or recurrent DTC. threshold has to be surpassed to achieve the cell death. This means The aim of the study was to evaluate the results of the radioiodine that a tailored radionuclide should exist that is able to provide the treatment in patients suffering from DTC and negative radioiodine desired therapeutic effect. The energy threshold depends on scintigraphy (RIS) but elevated serum Tg levels. several chemical/ biochemical factors (carrier molecule, target The study group included 78 patients treated in our hospital affinity, cell distribution, biokinetics, route of administration, between 2000 and 2004, age range 18-74 years, 57 papillary and radiation safety, etc.) although the radionuclide properties play 21 follicular thyroid cancer. All of them underwent a total or near one of the most important roles. Different half-lives imply total thyroidectomy and received 50-100 mCi I-131 therapy for different dose rates, resulting in very different clinical response for ablation and a second dose approximately 25% higher than the a given total dose if the surviving cells in the irradiated volume are first one. After a negative RIS (5 mCi of iodine-131) for continuously proliferating, and the sub-lethal damaged cells can metastases or thyroid bed remnants and serum Tg>3ng/ml (after be repaired during the protracted dose delivery. Therefore the thyroxine withdrawal and thyroid-stimulating hormone level principles of radiobiology, dose rate and absorbed radiation doses more than 30ìIU/ml) the patients received an empiric dose of are the most important in order to predict the radiation effects. 100mCi of iodine-131; 14 patients were administered >100 mCi Radionuclide selection for TR should not be solely based on their because lymph node metastases or pulmonary metastases were availability, but on an analysis of what would be best in terms of seen on ultrasonography , Rx, CT. Patients were followed-up by radiobiology. physical examination, Tg and RIS every 6 months or yearly for World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 56. S-50 Abstracts: ICRT-2005 (48%) patients (lymph node metastases in 27 patients, pulmonary score. Significant improvement of life quality was seen in 4 metastases in 11 patients).The RITS of the patients who received patients with major reduction of analgesic needs. In 4 patients in two or more doses showed improvement in 16 patients ( normal addition to external beam radiotherapy we obtained a stable effect scan or lesser activity than in the previous RITS), there were no of more than 6 months. 3 patients had moderate response, one of changes in 14 patients and in 6 patients the disease progressed. them with an early need of a second dose at four months. No The pre-treatment serum Tg level was 3-1584 ng/ml; no important response was seen in one patient. Pain flare occurred in 7 cases variations of the Tg level were observed during follow up; (58.3%). The most serious side effect noticed at these patients was however, in 12 patients Tg decreased, in 57 remained at the same myelosuppression, which occurred in 9 patients (75%), 2 of them level and in 9 patients serum Tg increased. Four patients died receiving transfusion. during follow up. Respecting the criteria of evaluating patients who might be As a conclusion in patients with negative RIS and elevated serum candidates for treatment using 89Sr, the significant clinical Tg levels, empiric treatment with radioiodine is recommended improvement of life quality can be obtained with an easy because post-therapeutic scans were positive in 48% of the procedure, controllable side effects and a good compliance of patients. The benefit of the empiric treatments with iodine-131 patient. In a country with limited resources for an extensive was demonstrated in the RITS of 16/36 patients that received two medical research it is important to introduce new strategies of doses at least. So, we think empiric radioiodine doses may be treatment that have proved their efficacy, to try to promote the cost successful administered in patients with previously RITS positive. effective use of high quality therapeutic procedures and the The negative RIS is possible to be caused by low dose of I-131 that recommended guidelines. is a poor imaging agent for the modern gamma camera so the detection of small or weakly iodine avid metastases is likely to be 085-RSA better at therapeutic doses. But the diagnostic dose cannot be Treatment of Hyperthyroidism with Radioiodine: comparison increased because of stunning. The alternative is to use I-123 for of the efficacy of low, medium and high doses of I-131, with diagnostic with better imaging properties, but unfortunately this is special emphasis on the socio-economic issues related to the not available in our country. treatment A. Ellmann et al 084-ROM Dept.of nuclear medicine, Tygerberg Hospital, 7505- Tigerberg, Use Of Sr-89 For Bone Pain Palliation: Experience In Our South africa Department Mititelu MR, Mazilu C, Rimbu A, Ghita ST, Marinescu G, Abstract not received Codorean I Central Clinical Emergency Military Hospital, Dept. of Nuclear 086-SER Medicine, Calea Plevnei 134, sector 6 Possible Role of the Scintigraphic Estimation of the Relative Bucharest, Romania Liver Perfusion in the Choice of Treatment of Liver Carcinomas Bone metastases are the most common cause of pain in patients Artiko V, Obradovic V, Davidovic B, Petrovic N, Vlajkoviæ M, with cancer, and postmortem studies have been shown that up to Kostic K 85% of patients with breast or prostate cancer have bone Institute for Nuclear Medicine, Clinical Center of Serbia and metastases at the time of death. The palliation of bone pain is one Department of Nuclear Medicine, Clinical Center Niš, Serbia and of the goals of treatments in oncologic patients, due to the fact that Montenegro patients with bone metastases may survive many years with severe pain and serious impaired mobility. Bone pain palliation can be In the preevaluation and diagnosis of the patients with liver attempt by using different modalities analgesics (nonsteroid, tumors, significant nuclear medicine methods used are: opioides), biphosphonates, external beam radiotherapy or radiocolloid, blood pool, hepatobiliary scintigraphy, radionuclide therapy. angioscintigraphy with radiolabeled microspheres as well as «first The aim of our study was to review the database and to analyze the pass» radionuclide angiography, which can preceede all of the results of the treatments performed in our department, in the field above mentioned methods, during single injection application. of radionuclide metastatic bone pain palliation with 89Sr The aim of the study is evaluation of the possible role of the 12 patients (47-73 years old) were treated with 89Sr in the past two scintigraphic estimation of the relative liver perfusion in the years in our department. All patients had confirmed prostate choice of treatment of liver carcinomas. adenocarcinoma and refractory bone pain due to skeletal The study was performed in 120 patients: 24 controls (C), 35 with metastasis involving more than one site, associated with benign liver tumors (BT), 35 with hepatocellular carcinomas osteoblastic response on bone scan. All patients had a good (HCC), 19 with metastases of colorectal carcinomas (MCC) as hematological and renal status (Hb> 9 mg/dl, leukocytes > 4000/ well as 7 with metastases of other tumors (MOT-bronhus, lung ìl, platelets > 150.000/ ìl, GFR > 30 ml/min), an increased alkaline carcinoma and lymphoma). 7/35 HCC had cavernous portal vein phosphatase and recent bisphosphonate therapy interrupted developed after tumor thrombosis, 2 had complete thrombosis and within 48h before treatment. The standard administered dose was 5 had incomplete thrombosis (thrombosis of the either of portal 150 MBq [4 mCi] of 89Sr (Metastron Amersham). In 8 cases venous branches (3) and incomplete portal venous thrombosis -2). single dose was given, while in 4 patients a second dose was 2/19 patients with MCC had cavernous portal vein developed after administered at 4, 6 and 9 months after the first injection. Clinical tumor thrombosis, 3 had complete portal venous occlusion and 4 and biological evaluation was repeated at 3 weeks and 3-6 months incomplete thrombosis (thrombosis of the either of branches). after treatment. Hematological assessment was performed The study was performed with ROTA scintillation camera and monthly at all patients. Micro Delta computer, during 60 sec (1f/sec) from i.v.application The most important criterion of pain relief was objective pain of 740 MBq 99mTc-pertecnetate. TA curves were generated using World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 57. S-51 Abstracts: ICRT-2005 liver ROI, spleen ROI and left kidney ROI, and curves were It is known that radioiodine treatment of benign thyroid diseases is generated. Hepatic perfusion index was calculated using slope accepted as a first line therapy in many nuclear medicine analysis (Portal slope Ps and arterial slope As) method according institutions but the methods, doses and eventual premedications to following formula HPI=Ps/(Ps+As). Complementary methods are still a matter of debate. In a number of institutions patients with used were Doppler ultrasonography, CT, MRI, tumor marker thyrotoxicosis are treated with anti-thyroid drugs before assays (CEA, Ca19-9, AFP) laboratory analyses, radioiodine therapy in order to deplete the thyroid gland of pathohistological finding and clinical diagnosis. preformed stores of hormones. Such approach may prevent In C, HPI was 0.68±0.06 which did not differ from the value in BT potential cardiovascular events particularly in elderly. This is (0.64 ±0.08) (p>0.05). However, in HCC ( X=0.26±0.20), and LM mostly true for patients with multinodular toxic goitre (MNTG). (X=0.40±0.28), HPI values were significantly decreased in Concerning the final 131I therapy outcome in these patients, comparison to C and BT (p<0.01), but they didn't differ between existing literature data are not sufficient and by some means themselves (H-LM, p>0.05). controversial. It is known that anti-thyroid drugs diminish serum In 7/35 HCC with cavernous portal vein developed after tumor levels of antithyroid antibodies and iodine uptake. In addition, thrombosis values were nonsignificantly lower (X=0.21±0.12, p some of them particularly those with sulfhydril group such as >0.05) than in HCC, in 2 with complete thrombosis values were propylthiouracil (PTU) may increase glandular radio resistance. significanly lower (HPI=0, p <0.01) and 5 with thrombosis of the The purpose of this analysis was to examine whether drug-free either of portal venous branches and/or incomplete portal venous period in patients with MNTG and treated with PTU is of any thrombosis values were significanly lower than those in HCC influence on the final outcome of radioiodine therapy. (HPI=0.17±0.09, p<0.05). In retrospective study, medical records of 300 patients (m=74, In 2/19 patients with MCC and cavernous portal vein developed f=226, mean age: 55 +/-12 years) suffering from MNTG and after tumor thrombosis, HPI was nonsignificantly lower than in treated with 131I where analysed. Patients were divided in two MCC (HPI=0.32±0.17, p>0.05), in 3 with complete portal venous groups. In group A were 120 patients (m=29, f=91) in which occlusion values were significantly lower than in MCC (HPI=0, therapy with PTU was withdrawn 4 to 6 weeks prior to 131I therapy. p<0.01) while in 4 thrombosis of the either of branches they were In group B were 180 patients (m=45, f=135) treated with the same significantly lower than those in MCC (HPI=0.25±013, p<0.05). drug incessantly up to the day of 131I therapy. Except for PTU all HRA could be easily done during the different conventional patients were using propranolol as adjuvant therapy. Two weeks nuclear medicine methods used in diagnostic process and in the prior to radioiodine therapy patients were instructed not to take pre-treatment evaluation. In addition, it can be an useful method iodine containing drugs and iodine-rich food. Water solution of 131I for the assessment of different degrees of hemodynamic (sodium iodide) was administered orally in an average doses of alterations in portal system, for differential diagnosis of benign 380 MBq (range 296-470). Clinical status and thyroid hormones and malignant liver tumors, as well as for assessment of the liver levels were assessed 3,6 and 12 months after the 131I therapy. At one tissue and tumor perfusion, which might be helpful in the decision year after the therapy patients were classified into three groups making for the undertaking of intraarterial 131I -lipiodol or 90Y- according to clinical status and serum levels of thyroid hormones colloid therapy. It is particularly suggestible because of the fact as hyperthyroidism (failure of the therapy), euthyroidism and that this therapy is mainly recommended in the unresectable and hypothyroidism. Thyrotropin (TSH), FT4 and FT3 were measured untransplantable patients with portal venous occlusion and mainly by DELFIA. All assays were calibrated against acknowledged arterial vascular supply. international reference standards. Thyroid iodine uptake was Thus, by this noninvasive method, it could be able to avoid measured 3h and 24h after per oral intake of 0.5 MBq 131I. Thyroid invasive and complicated (especially in the patients with impaired volumes were estimated by palpation and ultrasound by one coagulation factors) recommended study of portal backflow by experienced thyroidologist. The differences between two groups injection of an iodinated hydrosoluble radiological contrast agent were assessed by the Student's t-test. Non-parametric rank tests into the splenic or superior mesenteric artery, which is a were used to evaluate differences in final outcomes amongst two preliminary study for the selection of the patients for 131I groups of patients. A p value of less than 0.05 was considered as ethiodized oil therapy. It could also be used for evaluation of the statistically significant. efficacy and safety of hepatic intraarterial injection of 131I iodized No significant differences were found between two groups of oil in the treatment of liver carcinomas in patients with impaired patients in terms of age, gender, volume of the thyroid and mean portal venous flow, for the evaluation of its effect on the tumor PTU doses (100 ± 25mg) prescribed. Before the therapy 131I uptake itself, as well as its effect on the tumor thrombi in the portal vein and levels of thyroid hormones were significantly lower in group which are also arterially vascularized. This method will also allow B, so all patients in this group were biochemically euthyroid. the selection of the patients on the basis of tumor vascularisation, Clinical status of patients from group A, one year after radioiodine and reject from the procedure those (minority) with therapy was as follows: failure of the therapy was found in 11 (9%) predominantly portal vascularisation, or mainly arterial but with patients (m=3, f=8), euthyroidism in 99 (83%) patients (m=22, insufficient supply. Also, this procedure will allow the exact f=77) and hypothyroidism in 10 (8%) patients (m=4, f=6). Clinical estimation of the portal venous occlusion, suggestible for the status of patients from group B, one year after radioiodine therapy procedure. was: failure was found in 32 (18%) patients (m=10, f=22), euthyroidism in 142 (79%) patients (m=32, f=110) and 087-SER hypothyroidism in 6 (3%) patients (m=3, f=3). Failure rate was Is drug-free period prior to radioiodine therapy decisive for significantly higher in group B as well as a lesser degree of treatment outcome in patients with multinodular toxic goitre? hypothyroidism. Significantly higher rate of hypothyroidism was Han R, Beatovic S, MarkovicS, Jaksic E found in group A. Patients were a bit more likely to be euthyroid Institute of nuclear medicine, Clinical Centre of Serbia, Belgrade, after 12 months if they were clinically and biochemically Serbia and Montenegro euthyroid on the day of radioiodine therapy. No patients developed thyroid related orbitopathy. Relatively low rate of World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 58. S-52 Abstracts: ICRT-2005 hypothyroidism in both groups of patients is most likely due to 089-SIN iodine uptake restricted only to hyper functioning tissues in the [Re(CO)3]-Chelates as Therappeutic Radiopharmaceuticals multinodular thyroid gland. for the treatment of Hepatocellular Carcinoma Following the results of this single and relatively uniform Saw MM et al therapeutic protocol, it may be concluded that euthyroid clinical Department of Nuclear Medicine, Singapore General Hospital, status was found in nearly the same proportion in both groups of Singapore patients, regardless of the premedication prior to radioiodine therapy. Higher failure rate in patients treated with PTU up to the Abstract not received day of radioiodine therapy could be explained by higher radio resistance of thyroid tissue but, in these patients hypothyroidism is 090-SIN less likely to develop. Although the exact role of premediaction Experimental therapy with P-32 for hepatoma with PTU in clinical practice is still unclear and needs further Goh A et al study, we suggest that such approach is advisable in patients with Department of Nuclear Medicine, Singapore General Hospital, MNTG particularly in older and with known or susspected Singapore cardiovascular disease. Abstract not received 088-SER P-32 Orthophosphorus in the Treatment of Polycythaemia 091-SIN Vera and Essential Thrombocythaemia Radioimmunotherapy of Refractory B-Cell Lymphoma Jaukovic L, Ajdinovic B, Jankovic Z, Pucar D Sundram FX et al. Instutute of Nuclear Medicine, Military Medical Academy, Department of Nuclear Medicine, Singapore General Hospital, Crnotravska 17, Belgrade Singapore Serbia and Montenegro Abstract not received Polycythaemia Vera (PV) is a clonal progressive myeloproliferative disease, which is characterised by an 092-SLK autonomous proliferation of marrow cells and can be treated by Evaluation of the Efficacy of Radiosynovectomy in phlebotomy and cytoreductive therapy. The aim of this study was Rheumatoid Arthritis and Haemophilic Arthropathy to review the radionuclide therapy using P-32 orthophosphorus in (CERAHA): First Results of an IAEA Co-ordinated Research the treatment of the patients with PV and Essential Project (CRP) Thrombocythaemia (ET). During past ten years 21 doses of P-32 Vereb M, Kaliska L. were administered in 15 patients mean age 61.4 years (43-77) with Department of Nuclear Medicine, Hospital Poprad, Banícka PV and ET. In all of them the diagnosis of myeloproliferative 803/28, Poprad, Slovakia and Department of Nuclear Medicine, disease PV or ET was confirmed by haematologists using standard Roosevelt Hospital, L. Svobodu 1, 975 17 Banska Bystrica criteria. Red blood cells volume meassuring using 99m Tc labelled Slovakia erythrocytes was performed to facilitate the diagnosis. Patients were considered for P-32 administrations after than they have The main objective of the study was to determine the therapeutic failed treatment by phlebotomy and chemotherapy. After efficacy of radiosynovectomy. Rheumatoid arthritis is a Chronic phlebotomy of 300ml fool blood if necessary, patients were or sub-acute, systemic inflammatory disorder principally injected by P-32 fixed dose activity of 3 mCi per m2, increased up involving the joints with peripheral symmetrical inflammatory to 5 mCi for the additional one, intravenously via canula to avoid non-suppurative arthritis. It usually has a prolonged course with extravasations. Full blood count in monthly interval was used for relapse and remissions. Haemophilia is a congenital blood disease monitoring the patients and asses the response to therapy. The that produces abnormal bleeding at musculoskeletal level. The average duration of disease between the time of establishing the origin of this abnormal bleeding is the lack of a coagulation factor, diagnosis and P-32 administration was 22 months. Among 15 Factor VIII for haemophilia A and Factor IX for haemophilia B or patients injected by P-32 orthophosphorus, in six of them two Christmas disease. The overall goals of therapy in rheumatoid doses of P-32 were administered in the median interval of 24.7 arthritis are: alleviation of pain, control of disease activity, months. Complete remission was observed in 11 patients and slowing down the rate of damage and improvement in the quality partial remission in four patients at the end of the first year of of life. On the other hand the aim of the orthopaedic treatment in therapy. There was no report of the development of acute haemophilic haemarthrosis is to avoid recurrence of the myelogenous leukemia in treated patients. Thrombotic events haemarthrosis by acting on the synovial membrane, by fibrosing were registered in 2 patients. It is concluded that administration of it, in addition to pain alleviation and improving the quality of life. P-32 was shown as effective, inexpensive and simple modality of Radionuclide therapy, commonly known as “Radiosy- disease control in patients with Polycythaemia Vera and Essential novectomy”, is a very useful procedure, which if used Thrombocythaemia. Closer cooperation between hematologists appropriately may form an effective tool in the management of and nuclear medicine specialists would be necessary in the follow rheumatoid arthritis and haemophilic haemoarthropathy. With the up of patients for adequate documentation of side effects and help received from the IAEA under the auspices of a coordinated complications due to P-32 treatment. research project, for the first time in our hospital we introduced radiosynovectomy in the year 2003. Until now, a total number of 40 patients of rheumatoid arthritis and one patient of haemophilic arthritis have been treated following a protocol designed by the IAEA under the CRP. The diagnosis of rheumatoid arthritis and haemophilic arthropathy was established by standard well World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 59. S-53 Abstracts: ICRT-2005 established findings of clinical examination and laboratory Y Octreotide for metastatic carcinoid also as outpatients. investigations. 12 patients received 90-Y colloid intraperitoneally for All patients underwent a two phase bone soft tissue scintigraphy to experimental treatment of carcinosis due to ovarian Ca in 2004 assess the inflammatory activity in the joints prior to therapy. A (scientific study protocol, not used routinely). radiosynovectomy team was formed in the hospital consisting of a Radionuclide therapy is genarally well acepted in Slovenia. nuclear medicine physician, orthopaedic surgeon and a Nevertheless more widespread use is restricted by poor co- rheumatologist. In our hospital in most instances the intraarticular operation and comunications with oncologists (bone pain procedures were performed by our consultant orthopaedic paliation), logistic problems (intraarticular injections in case of surgeon. rheumatiod arthritis patients), lack of proper radiotherapy wards The results are now being analysed. Although we have seen good (all 131-I therapies above 550 MBq) and high cost (e.g. 90-Y anti results in most of our patients along with significant improvement CD20 MoAB). in quality of life, the rheumatologists and orthopaedic surgeons of our hospital are still inclined to perform surgical procedures over O94-SLO radiosynovectomy. The procedure of Radiosynovectomy is The Efficacy of Radiosynoviectomy in Hemophilic simple requiring only minor intervention. It is less expensive than Hemarthrosis According to the Frequency of Joint Bleedings any other therapy. It can be performed on an out-patient basis and Grmek M*, Brecelj J**, Fettich J* can be effective in those patients who are refractory to medical *Dept for Nuclear Medicine, **Dept. for Orthopedic Surgery; therapy, as well as in those who are not suitable for surgical University Medical Center Ljubljana, Slovenia therapy. The procedure does not require any rehabilitation process; it is possible to treat multiple joints simultaneously or at Radiosynovectomy is a potentially effective method for treatment short intervals. It is therefore recommended as an important mode of recurrent hemarthrosis in patients with hemophilia, and can of treatment in patients of painful arthropathy. It is hoped that with prevent the onset of hemophilic arthropathy. time this procedure will gain more and more acceptance in our Aim: to ascertain the effectiveness of radiosynovectomy in region and get integrated into the routine health care system to patients suffering from hemophilic hemarthrosis, to determine the benefit more and more needy and deserving patients suffering effect of treatment on clotting factor consumption, and to find out from painful joints. how the patients experience radiosynovectomy. 26 radiosynovectomies were done in 21 patients. Four joints were 093-SLO treated twice and one patient had 2 joints treated at the same time. 90 Radionuclide Therapy in Slovenia Y colloid was used for the knee joint (8 joints) and 186Re colloid Fettich J. for ankle, shoulder and elbow radiosynovectomy (18 joints). The University Medical Centre Ljubljana, Slovenia patients were followed for one year after therapy using a questionnaire. In Slovenia 1260 radionuclide therapies are performed per year During the first year following radiosynoviorthesis as compared for a population of 2 000 000 (63/100 000 inhabitants). to the year prior to the therapy the outcome of treatment was Approximatelly half of the patients (691) were treated as excellent in 11%, and good in 42% of cases. The number of outpatients. There are 7 nuclear medicine departments in the hemarthroses fell from 13 ± 8 to 7 ± 6 per year, and the country and 4 of them are licensed to perform radionuclide therapy consumption of the clotting factor declined by 13,200 I.U./year on and two have specialised wards for patients receiving radionuclide the average. In joints with 12 or more bleedings the number of treatment (10 beds). hemarthroses fell from 21 to 7 on the average. The outcome of 131-I is used by far most commonly for benign thyroid diseases treatment was excellent in 25%, and good in 37% of cases. A mean and differentiated thyroid Ca treatment. The patients receiving decrease in clotting factor consumption in the group was 25,800 doses of radioactivity below 550 MBqs, i.e. mostly patients with I.U. In joints with less than 12 bleedings, the number of bleeding Graves´ disease, are treated as outpatients i.e. 610/year, (31/100 episodes declined by 1, and the saving effected in the consumption 000 inhabitants). The patients treated with doses between 740 of clotting factor was negligible. After the treatment, 55% of 1110 MBq, mostly hyperthyroid patients with autonomous thyroid patients had no adverse reactions; 37% had mild transitory tissue (Plummer´disease), 300/year (15/100 000 inhabitants) are swelling and 7% developed moderate transitory swelling of the hospitalised for 3 5 days in a speciaised wards. (Fractionated treated joint. therapy is not used). It was concluded that radiosynovectomy is an effective method for 137 therapies were performed for ablation and treatment of the treatment of hemophilic hemarthrosis, particularly in patients metastases in patients with differentiated thyroid cancer receiving with frequent intra-articular bleedings. In patients with frequent 1850 5550 MBq, in 2004 as inpatients. bleedings into joints the consumption of the clotting factor was 131-I mIBG is used for treatment of neuroblastoma very reduced significantly only. Radiosynovectomy is well accepted by occasionally, less than 1/year due to low number of patients. Such patients suffering from hemophilic hemarthrosis. patient has to be hospitalised in an adult radiotherapy ward, a situation not prefered by paediatritians. 095-SLO 186-Re HEDP, 153-Sm EDTPM and 89-Sr were used for paliation Recombinant Human TSH (rhTSH)- Aided Radioiodine of bone pain due to bony metastasis usually as outpatients, Therapy in patients with metastatic differentiated thyroid depending on patient´s condition, in only 14 patients in 2004. carcinoma Results 2002-2004 186-Re colloid and 90-Y colloid are used for radiosynovectomies Schwarzbartl-Pevec A1, Vidergar-Kralj B1, Zagar I1, Besic N2 in patients with rheumatic and (32/year) and hemophilic (25/year) 1 Department of nuclear medicine, 2 Department of surgery, arthropathies. These patients are not hospitalised. Institute of Oncology, Ljubljana, Slovenia 5 patients were treated with 90-Y anti CD20 MoAB for NHLymphoma, all on outpatient basis and 2 patients received 90- A serum TSH level of > 30 mU/L, which is necessary for reliable World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 60. S-54 Abstracts: ICRT-2005 testing and efficient radioiodine therapy in patients with examination at presentation, pelvic US and CT of the abdomen differentiated thyroid carcinoma, may be achieved by: a 4-6 weeks revealed a new tumor in the ileocecal region. Its primary origin in L-thyroxine withdrawal or by application of recombinant human the gastrointestinal tract was ruled-out by gastroscopy and TSH (rh TSH).The purpose of our study was to test the efficacy of colonoscopy. Explorative 131-I therapy (RAIT) using recombinant human TSH (rhTSH) as laparotomy revealed a right-sided tumor of the omentum, a 2.5 cm an alternative in patients with differentiated thyroid carcinoma large lymph node in the ileocecal part of the omentum and (DTC) in whom endogenous TSH stimulation was not an option additional smaller lesions, upto 2 cm in diameter, disseminated due to the poor patient's physical condition during the hypothyroid througout the abdomen these were histologically proven to be state or due to the disease progression during L-thyroxine metastases of a well-differentiated, follicular thyroid carcinoma. withdrawal. A 14 x 18 mm large nodule in the right thyroid lobe was The study comprised 14 patients (12 females, 2 males, aged 63- ultrasonographically, scintigraphically and cytologically non- 81, median 73 years), with histologically proven DTC, in whom suspective of malignancy. the primary diagnosis was established 1993-2000, who already Taking into account the abdominal metastatic spread, the primary have undergone total or near-total thyroidectomy and who have follicular carcinoma in the thyroid gland seemed less probable received radioiodine ablation and 3-12 (median 6) RAITs after L- than the primary arising from struma ovarii. thyroxine withdrawal, with a cumulative dose ranging 15.65- Extensive surgical removal of the abdominal metastases was 68.34 GBq. followed by the near-total thyroidectomy, that revealed no Patients were given 28 RAITs (7/14 patients received two, 2 evidence of malignancy in the thyroid tissue thus making the received 3 and 1 received 4) while on L-thyroxine after rhTSH struma ovarii more probable and by ablation with 3.7 MBq 131-I. administration (rhTSH RAIT). RhTSH (0.9 mg, i.m.) was Post-ablation WBS (at TSH > 30 mU/L, Tg 9.5 ng/mL and anti-TG administered on two consecutive days, followed by 131-I antibodies 173.78 U/mL) has shown 131-I uptake in thyroid tissue therapeutic dose (5.2-7.6 GBq) administration on the third day and remnants bilaterally and pathologic tracer uptake in the mid- and a post-therapeutic whole-body scan (PTWBS) 2-5 days later. The left hypochondrium, right mesogastrium and median and right efficacy of rhTSH RAIT was evaluated by thyroglobuline (Tg) pelvis. Thyroglobulin value 3 months after RI ablation, both while measurement 3 - 6 months after rhTSH RAIT. on L-thyroxine suppression and under endogenous TSH Serum TSH levels after rhTSH administration were 61 - 305 mU/l. stimulation, preceding second (therapeutic) 131-I application, Altogether 36 131-I-avid lesions were detected on PTWBS. In one were 0.2 ng/mL, however with high anti-TG antibody titres patient who underwent two rhTSH RAITs a decrease of 131-I (507.63 and 277.8 respectively). uptake in one lesion was seen on the second PTWBS. In all A post-therapeutic WBS, 48 hrs post 5.5 GBq 131-I and 4 months patients serum Tg concetrations were elevated before rhTSH after ablation, has again shown faint uptake in the thyroid tissue RAIT (25 -17248 ng/ml). Three months after therapy serum Tg remnants, but demonstrated a complete regression of the intra- decreased by 24 -91% in 6 cases (4 patients), in 3 patients serum abdominal lesions. Tg stagnation was achieved, while in 7 cases the disease The patient is now, during a 16 months follow-up period after the progressed (serum Tg increased upto 131 - 190% baseline level ). last radioiodine application, euthyroid. She is clinically and The rhTSH was well-tolerated. Two patients had mild nausea biochemically with no evidence of the disease. The case and/or headache, two experienced pain in the bone metastases, demonstrates the necessity of combined surgical and radioiodine another two experienced a “flu-like syndrome”. treatment in malignant struma ovarii and the importance of long- It is concluded that RhTSH RAIT may be effective in metastatic term follow-up after the initial surgery. DTC patients who otherwise could not be efficiently treated with 131-I. However, the diversity of other therapeutic approaches 097-SRL (previous RAITs under endogenous TSH stimulation, external- Radioiodine (I-131) application in the management of beam radiotherapy, chemotherapy) even in a well-responding differentiated thyroid cancer (DTC) Audit patients did not allow us to attribute the tumor and metabolic Nanayakkara D response just and only to the RAIT under rhTSH stimulation. Nuclear Medicine Unit, Faculty of Medicine, University of Peradeniya, Sri Lanka 096-SLO Differentiated thyroid cancer (DTC) remains one of the curable of Another case of Metastatic Malignant Struma Ovarii? A case all cancers. All literature reviews and clinical experiences report of good response to Radioiodine Therapy regarding I131 use in DTC conclude the beneficial effects, better Žagar I1, Vidergar-Kralj B1, Schwarzbartl-Pevec A1, Besic N2 prognosis, longer survival time and an assurance for cure. The 1 Department of Nuclear Medicine, Institute of Oncology Overall prognosis of patients with DTC is excellent if treat Ljubljana, Slovenia and 2Department of Surgery, Institute of scientifically, adequately and timely. The management of thyroid Oncology Ljubljana, Slovenia cancer depends on the resources available in different institutions. Nuclear Medicine unit (NMU), Faculty of Medicine Peradeniya, Sri Lanka is in the process of uplifting the services for thyroid Struma ovarii is a rare ovarian germ-tumor, consisting mainly of cancer management. Clinical audit was carried out in NMU on thyroid tissue, comprising up to 2% of all ovarian tumors. In 2-5% patients who utilized the Nuclear Medicine facilities in the of all cases it is malignant. Approximately 5% of all malignant management of DTC. It is important to identify deficiencies in ovarian strumae metastasize, mainly to the peritoneum and liver. current practice to improve our services. We report a case of a 59-years-old female, who presented with During January 2004 to March 2005, 126 DTC patients were vague abdominal pain. She had a history of an abdominal referred for radioiodine Whole body scan (WBS) and therapy. operation at age of 39 (when 3 months pregnant) for a septated Their age, sex, histology, extent of surgery, adequacy of thyroxine cystic ovarian tumor in the ileocecal region, that contained a suppression treatment, monitoring with serum thyroglobulin dermoid cyst. Neither the definite histopathological finding, nor levels (Tg), WBS results and radioiodine therapy were analyzed. the TG value at the time of operation were available. Physical There were 104(82.5%) females and 22(17.5%) males giving sex World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 61. S-55 Abstracts: ICRT-2005 ratio of 4.7: 1. The Mean age was 35.5 years (range 9-58 years). 099-UK The commonest histological types were papillary carcinoma Pathophysiology and non-radionuclide therapy of 55.5% (n=70), follicular carcinoma 35% (n=44) and follicular neuroendocrine tumours variant of papillary carcinoma 9.5% (n=12). Seventy five percent Buscombe J (n=95) had total thyroidectomy (TT), 17 %(n=21) had near total Royal Free Hospital, Dept. of Nuclear Medicine, Pond Street, thyroidectomy (NTT) and 8%(n=10) had subtotal thyroidectomy Hampstead, London NW3 2QG, United Kingdom (STT). Sixty-nine patients (54.8%) were on thyroid suppression therapy. Thirty-six patients (28.6%) were referred to the WBS soon after surgery without initiation of thyroxine treatment. Abstract not received Another twenty-one patients (16.6%) were not on thyroxine therapy since surgery. Serum thyroglobulin was assessed on 100-UK 20.6% (n=26). WBS done using 3-4 mCi liquid radioiodine Problems with antibody treatment of solid tumours showed residual functioning thyroid tissues in 41% (n=52). Buscombe J Lymph nodes or bone metastases were detected in 16% (n=21). Of Royal Free Hospital, Dept. of Nuclear Medicine, Pond Street, 52 patients with residual thyroid tissues, fourteen patients (30%) Hampstead, London NW3 2QG, United Kingdom received residual ablation dose of 30 mCi of radioiodine. All 21 patients who exhibit abnormal WBS were referred to the cancer Abstract not received unit for high dose therapy. This study showed DTC is more common in young females than in males and Papillary carcinoma is the commonest histological type 101-UK in Sri Lanka. Though the preferred surgical management is TT or Use of I-131 Lipiodol for the treatment of liver cancer: NTT (92%) this study showed inadequacy of excision. In Sri A Review Lanka we have very few experienced thyroid surgeons. Buscombe J Inadequate surgical excision could be due to inexperience and lack Royal Free Hospital, Dept. of Nuclear Medicine, Pond Street, of facilities for surgical management in peripheral hospitals. Hampstead, London NW3 2QG, United Kingdom Inadequate surgical excision will directly interfere with the long- term follow up of DTC. Presence of remnant thyroid tissues makes Abstract not received detection and treatment of nodal or distant metastases difficult. High TSH levels necessary to enhance tumor I131uptake and assessment of Tg levels, the most sensitive test for detection of 102-UK recurrences cannot be achieved with a large thyroid remnants. Use of Y-90 lanreotide and Y-90 microsheres in treatment of This results indicative of low sensitivity of the WBS and serum Tg liver tumours measurements in our set up. We have detected 16% of patients Al-Nahhas A et al with distant metastases but the actual number may be higher than Department of Nuclear Medicine, Hammersmith Hospital, Du this figure. Monitoring with Tg is grossly inadequate. Serum Tg Cane Road, London WI3 0HS, UK test is expensive in our set up prevent us using this facility. Approximately 2/3 of this study group were not received residual Abstract not received ablation partly due to unawareness, not enough radioiodine in the government hospitals and poor follow up in our set up. 103-UK Management of DTC is still debatable. There is no agreement on Radiolabelled Aptamers for Tumour Imaging and Therapy extent of surgery, optimal time for WBS, residual ablation and long-term fallow up. Today highly effective method of treatment Perkins AC1, Missailidis S2 1 for DTC is the combination of thyroid surgery (TT/NTT) followed Dept of Medical Physics, Medical School, University Hospital, by RAI residual ablation and thyroxine suppression therapy. 30 Nottingham, NG7 2UH; 2Dept of Chemistry, The Open mCi of radioiodine is the highest permissible activity for out University, Walton Hall, Milton Keynes, MK7 6AA, UK patient treatment according to the local Atomic Energy Agency, Sri Lanka. We prefer to use 30 mCi RAI for residual ablation as it The growth in biotechnology has led to new techniques for the can be used effectively on an out patients basis with associated low design, selection and production of ligands capable of molecular cost, convenience and low whole body radiation absorbed dose to recognition. One promising approach is the production of specific the patient. Review of current practice in time to time is justified. Several receptor binding molecules based on specific nucleic acid deficiencies in the management of DTC as a whole were sequences that are capable of recognising a wide array of target identified. Extent of surgery, radioiodine residual ablation, TSH molecules. These oligonuclide ligands are known as aptamers suppression after surgery and monitoring with serum Tg are (1.2). The technology that allows production of aptamer grossly inadequate. Guidelines should be introduced to promote molecules is known as systematic evolution of ligands by the cost effective use of Nuclear Medicine facilities in the exponential enrichment (SELEX). We have used combinatorial management of DTC. Locally agreed protocols are needed to chemistry techniques coupled with polymerase chain reaction minimize these deficiencies and uplift the existing facilities in the (PCR) to rapidly select aptamers from degenerate libraries that diagnosis, treatment and follow up of DTC patients in Sri Lanka. bind with high affinity and specificity to the protein core of the MUC1 antigen, a tumour marker previously extensively used in 098-THA tumour imaging and therapy. MUC1 is widely expressed by First Experiences in 90Y-Zevalin For Treatment of Non- normal glandular epithelial cells, however this expression is Hodgkin's Lymphoma in Thailand dramatically increased when the cells become malignant. This has Saesow N et al. been well documented for breast and ovarian cancer, as well as Division of Nuclear Medicine, Department of Radiology, Faculty some lung, pancreatic and prostate cancers (3). Recently it has also of Medicine, Chulalongkorn University, Bangkok, THAILAND- been shown that MUC1 is a valuable marker for bladder and has 10330 been used for the imaging and targeted therapy of bladder cancer. The aptamer selection process was performed on affinity Abstract not received World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 62. S-56 Abstracts: ICRT-2005 2 chromatography matrices. After ten rounds of selection and Center for Experimental Radiation Oncology, Cancer Care amplification, aptamers were cloned and sequenced. Post SELEX Center, St George Hospital, Gray St, Kogarah 2217, NSW, amino modifications have been used to confer nuclease resistance Australia and coupling potential. The aptamers bound to MUC1 antigen with a Kd of 5nm and high specificity, demonstrated by Mucins are high molecular-weight heavily glycosylated fluorescent microscopy on MUC1-expresing tumour cells. Using glycoproteins with many oligosaccharide side-chains, linked to a peptide coupling reactions, we have successfully attached protein backbone called apomucin. A total of 19 different mucin chelators for Tc-99m radiolabelling. Two of the constructs tested genes (MUC1-MUC4, MUC5B, MUC5AC, MUC6-MUC18) were based on mono-aptamer chelator complexes, one with have been identified to date. Mucins are present on the surface of commercially available MAG3 and one with a novel designed most epithelial cells and play a role in their protection and cyclen-based chelator. The other two constructs were based on the lubrication. In cancer cells the mucin molecule becomes altered, use of multi-aptamer complexes, where four aptamers were thus representing an important target for diagnosis and therapy. attached to the four arms of either DOTA or carboxy-porphyrin. Urinary epithelial mucin1 (MUC1) is found to be frequently The four complexes were labelled with Tc-99m and tested for their upregulated and abnormally glycosylated in a number of common efficacy as tumour imaging agents. All four complexes malignancies, including breast, bladder, colon, ovarian and gastric demonstrated specificity for the tumour, due to their MUC1 cancer. specificity, at various levels. Biodistribution studies were carried The monoclonal antibody C595 is an IgG3 murine MAb raised out in mice with MCF7 xenografts. The monomeric aptamer against the protein core of human MUC1 (1). Epitope mapping has complexes had rapid renal clearance from the system, due to their shown that C595 recognizes a tetrapeptide motif (RPAP) within small size (MW of 8,000 Da). More than 90% of the aptamer based the protein core of MUC1 mucin that contains a large domain of radiopharmaceutical was cleared from the system within the first multiples of a highly conserved 20-amino-acid-repeat sequence 15 minutes. To increase retention time, additional constructs based (PDTRPAPGSTAPPAHGVTSA). This antibody has previously on the design of a tetra-aptamer complex were prepared. A core been radiolabelled with 99mTc and 111In and used for imaging a range chelator, such as DOTA and carboxy-porphyrin has been used as a of tumour types including ovary, breast and bladder. The antibody skeleton for the building of multiaptamer constructs aiming to has also been radiolabelled with 67Cu and 188Re for the therapy of increase the molecular weight of the complex and potentially its superficial bladder cancer. stability of binding due to interactions with more than one MUC1 More recently we have investigated the pre-clinical use of the molecules at the surface of the tumour cell. The increase of the C595 antibody for targeted alpha therapy using 213Bi which emits MW to 32,000 Da allowed increased retention times in the system, alpha particles with high linear energy transfer (LET), short range without compromising the exceptional tumour penetration ( 80 m) radiation and has a short physical half-life of 45.6 minutes. exhibited by all the aptamer based constructs under study. Alpha particles are some 7300 times heavier than beta particles The development of aptamers as small building blocks for and in theory, following binding of an alpha immunocongugates to targeting agents offers several advantages. These molecules the target, a large fraction of the alpha particle energy is delivered penetrate tumour more readily than whole antibodies, reach peak to cancer cells, with minimal concomitant radiation of normal levels in the tumour more rapidly and clear from the body faster, tissues. 213Bi was produced from the 225Ac/213Bi generator. For thereby reducing toxicity to healthy tissues. Our strategy is to antibody conjugation the chelator, cyclic diethylene- manipulate the molecular weight of the construct utilising triaminepentacetic acid anhydride (DTPA) was used. Initial previously devised methodologies to achieve various polymeric experimental studies have concentrated on the targeted therapy of aptamer complexes in order to acieve the optimum balance carcinoma of the prostate, pancreas and ovary. between the low immunogenicity and excellent tumour On 120 paraffin embedded specimens from patients who penetration. In this way we aim to achieive a balance against the underwent radical retro-pubic prostatectomy or trans-urethral- rapid renal clearance that leads to premature elimination of the resection of the prostate for primary untreated carcinoma of the complex from the system and adequate tumour uptake for pancreas MUC1 expression was detected in 58% primary Ca diagnostic imaging and targeted therapy. We intend to undertake protate tissues and 90% lymph node metastases but not in normal further work using Re-188 to produce a therapeutic aptamer prostates or benign tissues. The 213 Bi-C595 conjugate conjugate. demonstrated cell killing in PC-3 and DU 145 cell lines isolated from human prostatic adenocarcinoma (2). Other results indicate References: that 213Bi-C595 targeting efficacy is in accordance with the 1. Jayasena S. D. Aptamers: an emerging class of molecules that expression of MUC1 in three pancreatic cancer cell clusters rival antibodies in diagnosis. Clin. Chem. 1999; 45:1628-1650. CFPAC-1, PANC-1 and CAPAN-1 and demonstrated effective 2. Guhlke S., Famulok M., Biersack H. J. Aptamers: A novel class toxicity of tumour spheroids of up to 100 m in diameter. When of radiopharmaceutical with diagnostic and therapeutic administered to tumour bearing mice at 333 MBq/kg the c595 potential. Eur. J. Nucl. Med. Mol. Imaging. 2003; 30:1441- alpha conjugate caused significant tumour growth delay, 1443. compared with the non-specific control at after 16 weeks (3). 3. Zotter S, Hageman PC, Lossnitzer A, Mooi WJ, Hilgers J. Similar results have been obtained in monolayers and cell clusters Tissue and tumor distribution of human polymorphic epithelial of the ovarian OVCAR-3 cell line. mucin. Cancer Rev 1988;11-12:55-101 We believe this antibody conjugate offers great potential for targeted alpha therapy of prostatic, pancreatic and ovarian 104-UK tumours. C595 Antibody: A potential vector for targeted alpha therapy Perkins AC1, Allen BJ2 References: 1 Dept of Medical Physics, Medical School, University Hospital, 1. Price MR, Pugh JA, Hudecz F, Griffiths W, Jacobs E, Symonds Nottingham, NG7 2UH, UK IM, Clarke AJ, Chan WC, Baldwin RWA monoclonal antibody World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 63. S-57 Abstracts: ICRT-2005 against the protein core of human urinary epithelial mucin detected (P < 0.05) following radioiodine therapy as compared to commonly expressed in breast carcinomas. Br J Cancer the control group. 1990;61: 681-686. 2. Li Y, Rizvi MA, Blair JM, Cozzi PJ, Qu CF, Ow KT, Tam PN, Indices Parotid Gland Perkins AC, Russell PJ, Allan BJ. Antigenic expression of Right Left human metatstic prostate cancer cell lines for in vitro multiple- Gr-I Gr-II P Gr-I Gr-II P targeted a-therapy with 213Bi-conjugates. Int J Radiat Oncol Cc 2.7± 1.4± 0.04 1.7± 1.3± 0.03 Biol Phys. 2004;60:896-908. 0.8 0.2 0.6 0.2 3. Qu CF, Song YJ, Rizvi SMA, Smith R, Perkins AC, A Ce 44.9± 33.1± 0.01 43.6± 28.6± 0.01 Morgenstern A, Brechbiel, M, Allen BJ. In Vivo and In Vitro 2.0 4.0 3.1 5.3 Inhibition of Pancreatic Cancer Growth by Targeted Alpha Tmax, 14.7± 9.3± 0.0043 14.1± 8.8± 0.004 Therapy using 213Bi-CHX.A"-C595. Cancer Biol, Ther. In min 1.0 1.5 1.0 1.5 Press 2005. Submandibular gland Cc 1.4± 1.2± 0.04 1.4± 1.2± 0.008 105-UK 0.4 0.5 0.4 0.5 Radionuclide Therapy Of Hyperthyroidism: An Over View Ce 32.5± 22.1± 0.0009 31.5± 22.8± 0.016 Vinjamuri S et al 2.0 2.3 2.6 2.6 Royal Liverpool University Hospital, Department of Nuclear Tmax, 12.7± 8.4± 0.015 12.4± 8.8± 0.037 Medicine, Prescot Street min 1.3 1.2 1.2 1.3 Liverpool L78XP, UK 108-UKR Abstract not received Radionuclide Therapy for True Polycythemia Afanasieva NI, Grushka GV, Vasiliev L Ya 106-UK Department of Nuclear Medicine, Grigor'ev Institute of Medical Radioimmunotherapy of Pancreatic Cancer with Monoclonal Radiology, Kharkiv, Ukraine Antibodies Vinjamuri S et al True polycythemia (Vaquez' disease) is the disease of the Royal Liverpool University Hospital, Department of Nuclear hemopoietic system of an unknown origin accompanied by Medicine, Prescot Street increase of erythrocyte count in the peripheral blood with absolute Liverpool L78XP, UK and relative increase in the mass of circulating erythrocytes. True polycythemia is treated with bloodletting and Abstract not received myelosuppressing drugs. This treatment is not always effective. A special place among myelo-depressants is occupied by P-32. Its 107-UKR main therapeutic effect is mediated by the participation in the Sialoscintigraphy With Tc-99m Pertechnetate In The metabolic processes. Besides DNA damage with beta-radiation, Evaluation Of Salivary Gland Function In Patients With P-32 incorporation by DNA followed by decay and transformation Differentiated Thyroid Cancer After Radioiodine Therapy to a stable sulphur isotope (S-32) results in the damage of the Korol P structure of nucleic acids, which is main mechanism of cellular Institute of Oncology, Academy of Medical Sciences of Ukraine, proliferation inhibition. Therefore, P-32 is considered a powerful Kiev, Ukraine. myelosuppressive agent. The indication to P-32 administration is true polycythemia, which, The aim of this study was an evaluation of salivary gland function in contrast to secondary polycythemia accompanying numerous after radioiodine therapy (RIT) in patients with differentiated diseases, requires special cytostatic treatment. thyroid cancer (DTC) using sialoscintigraphy with Tc-99m The study involved 152 patients with true polycythemia (76 men pertechnetate. We investigated 97 patients with thyroid cancer and 76 women aged 48) treated with P-32. The treatment was aged from 35 to 65 years. The patients were divided into two administered in case when bloodletting proved to be ineffective groups. First group consisted of 30 patients after total or subtotal and hematocrit level exceeded 75%. P-32 was administered orally thyroidectomy without RIT and symptoms of functional activity in 100 ml of 10% glucose solution on an empty stomach at a dose changes of salivary glands. Second group included 67 patients of 37-111 MBq with a 4-10-day intervals (mean 6 days). The blood after thyroidectomy and following RIT. Administered therapeutic count was checked for 12 weeks. If the number of thrombocytes activities varied ranging from 1100 to 4720 MBq. We performed and leukocytes decreased less than by 25% and the level of sialoscintigraphy in dynamic mode over a period of 30 minutes (1 hematocrit did not normalize, repeated P-32 treatments were frame per 20 sec) with stimulation of gland function at 20 min of performed. study using lemon juice. For evaluation of salivary gland function In 13 (8.6%) patients, haematocrit parameters became normal we used wide spectrum of indices and activity-time curves after a single P-32 administration, in 15 (9.9%) patients two obtained from zones of interest “salivary glands”. From among the treatments with P-32 were necessary to normalize the blood count. large number of indices determined in the study we could identify In 134 (88.1%) cases P-32 treatment was administered more then three most informative indices. These are 1. Coefficient of two times (maximum 10 treatments). Total P-32 activity ranged concentration (Cc), coefficient of excretion (Ce) and T-max. The from 37 to 740 MBq. Of all the patients who were administered P- mean values of all of these indices were significantly decreased in 32 treatment, hematological remission was achieved in 102 the patients belonging to the second group in comparison with first (67%). In these patients, the general condition improved, angina group. These are outlined in the following table: and thrombophlebitis course became more favorable, and ability Overall significant decrease in salivary gland function was World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 64. S-58 Abstracts: ICRT-2005 to work improved. Mean remission duration after the first course tumor process dissemination, DGT can stabilize the tumor of treatment with P-32 was 42 months and 26 months after two growth. courses. Mean life span made up 9.3 years. On the other hand, DGT is not indicated in case of radical surgery Thus, radionuclide therapy for true polycythemia with P-32 or in children, even with an extended tumor process. In this case, improves the quality of life and increases mean life span in the the protocol of treatment includes surgery followed by I-131 patients. therapy. External irradiation should not be performed, if a pronounced therapeutic effect is not expected. In other words, 109-UKR gamma-therapy is advisable only when surgery and I-131 Up-to-Date Program of Treatment and Long-Term Follow-up treatment have proven to be ineffective. of the Patients with Differentiated Thyroid Carcinoma The purpose of a long-term follow-up is revealing locoregional Afanasieva NI, Grushka GV, Astapieva OM relapses and distant metastases. The patient examination is based Department of Nuclear Medicine, Grigor'ev Institute of Medical on combined use of clinical examination, echography of the neck Radiology, Kharkiv, Ukraine region, thyroglobulin (Tg) level assessment in the blood serum, whole body scan with residual activities using I-131 natrium Primary treatment for thyroid carcinoma depends on the process iodide. Increased Tg level is considered to be the only sign of dissemination and disease prognosis. The former includes 1) thyroid cancer metastases in the operated patients, even when the surgery, which is the first and chief method of treatment almost in findings of clinical, x-ray and scintigraphic studies are negative. all cases; 2) I-131 natrium iodide treatment following surgery to Comparison of sensitivity of diagnostic scintigraphy with I-131, achieve ablasticity of the residual tumor tissue, which is especially sonography of the neck and assessment of Tg level in the operated in some cases; 4) inhibiting hormone therapy is important, if patients after radioiodine ablation of the residual thyroid tissue unfavorable prognostic factors are present; 3) distant radiation suggests that laboratory study of Tg level correlates with the therapy is possible. clinical state of the patients and the findings of isotopic techniques The criteria for determining the volume of surgery are the size, in 99.5% of the patients. morphology, character and rate of During dynamic observation it is necessary to control TSH level growth of the tumor, presence of regional metastases and their for adequate hormone therapy with the purpose of inhibiting mobility, age of the patient, signs of invasion to the adjacent thyrotropin secretion to prevent relapses and metastases of the organs. From oncology perspective, minimum volume of thyroid tumor. intervention in tumors > 2 cm is extrafascial hemistrumectomy, when the tumor is located in the lateral portions; extrafascial 110-UKR hemistrumectomy with removal of the isthmus and resection of Combination Radiation Therapy for Bone Metastases in the adjacent 1/3 of the neighboring tumor tissue, when the tumor is Thyroid Cancer located in the center and medial portions of the lobe or in the Afanasieva NI, Grushka GV, Muzhychuk OV, Astapieva OM isthmus. Department of Nuclear Medicine, Grigor'ev Institute of Medical Thyroidectomy is a method of choice in large tumors. This allows Radiology, Kharkiv, Ukraine avoiding development of bilateral cancer, local relapses as well as improving survival and reducing the death rate. Thyroidectomy Distant metastases of thyroid carcinoma (TC) occur due to facilitates I-131 treatment and increases sensitivity of dissemination of cancer cells through the lymph and blood radionuclide body scan with the use of I-131. Diagnostic vessels. They develop in 10-15% of patients with differentiated determining of thyroglobulin for revealing the tumor metastases is thyroid carcinoma and are the main cause of death in cancer possible only after thyroidectomy. patients. Appearance of distant metastases depends on a number of Treatment with I-131 sodium iodide is the second essential stage factors, i.e. the age of the patients (chiefly in children and those of multimodality treatment for thyroid carcinoma. Multifocal over 45); small size tumors; invasive growth of the tumor outside differentiated cancer is found in 20-30% of the patients; residual the thyroid capsule; involvement of the sentinel lymph nodes; thyroid tissue, the source of thyroglobulin, reduces informativity poor differentiation of the tumor; incomplete surgical removal of of the tumor marker determining; the residual thyroid tissue, as a the tumor. rule, competes with the relapses and metastases of thyroid cancer Distant metastases mainly localize in the lungs and/or bones. In for I-131 absorption; hidden distant metastases of thyroid thyroid cancer patients with suspected bone metastases the latter carcinoma can be revealed by I-131 scan only on complete are revealed radiologically on the primary examination ablation of the residual thyroid tissue. All these prove for I-131 (approximately in 95.9% of cases). In 25% of them, they are seen treatment with the purpose of ablation of the residual tumor tissue. at body scan with I-131 on residual activities. Probability of In the post-operative period, I-131 treatment is indicated in case of visualization of iodine-positive bone metastases is higher at non-radical surgery, or when the radical charter of the surgery is ablation of residual thyroid tissue. When the metastases are doubtful. The advantages of this approach have been revealed by x-ray study, they cannot be treated using I-131, which demonstrated by the reduction in the incidence of relapses and emphasizes the necessity of other methods of treatment: surgery increase of the life span. and distant radiation therapy. But due to multiple character of bone According to the international experience and the standard metastases surgery for these metastases is impossible. treatment protocols for differentiated thyroid cancer, planned Within the period of 1999-2004 we studied 310 patients with distant gamma-therapy (DGT) is considered unexpedient due to differentiated TC aged 22-72 (of them 254 women and 56 men). low sensitivity of the tumor tissue. DGT can be indicated in case of Bone metastases were revealed in 15 (4.8%) patients, of them 13 incomplete or doubtful surgery, especially in elderly patients with women and 2 men aged 46-68. As to the stage of the tumor with poorly differentiated tumor, in case, when the tumor is poorly bone metastases, the patients were grouped as follows: T1N0M0-1 differentiated and I-131 absorption is inconsiderable or (6.7%), T2-3N0M0-1 (6.7%), TxNxMo-4 (26.7%), T1-4N0-1M1-9 completely absent. In case when surgery is not possible due to the (60%) patients. World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 65. S-59 Abstracts: ICRT-2005 Of the 15 patients with bone metastases, papillary cancer was Korea; 3Fundación Cardioinfantil, Bogotá, Colombia. verified in 5 (33.3%) patients, follicular in 5 (33.3%) papillary 4 cancer follicular variant in 1 (6.7%), medullary in 4 (26.3%). Technische Universitaet Dresden, Dresden, Germany; Together with bone metastases, 5 (33.3%) had metastases to the 5 Cerrahpasa Medical Faculty, Istanbul, Turkey; 6Instituto de lung parenchyma, diffuse and solitary; 12 (80%) had metastases to Cardiología y Cirugía Cardiovascular, Havana, Cuba; sentinel and distant lymph nodes. 7 Pomeranian Academy of Medicine, Szczecin, Poland; The presence of bone metastases was revealed using x-ray study 8 Semmelweis University of Medicine, Budapest, Hungary; 9Oak and confirmed using bone scan with Tc-99m pyrophosphate. Ridge National Lab, Oak Ridge, TN, USA; 10Division of Human During the treatment the patients with bone metastases were Health, Nuclear Medicine Section, IAEA, Vienna, Austria. administered 1480-14,134 MBq of I-131. Of all patients with bone Intravascular radiation therapy (IVRT) using a standard metastases, bone metastases accumulated I-131 only in 4 (19%) angioplasty balloon filled with 188Re-perrhenate has been shown to patients. reduce the risk of restenosis after PTCA. This strategy can Thus, treatment of TC with bone metastases only with I-131 did constitute a cost-effective, self-centering approach. The purpose not produce a desirable palliative effect as well as did not control of the present study was to evaluate the safety and effectiveness of the progress of metastasizing. Therefore, together with I-131 this technique in the framework of a prospective, multi-center and treatment the patients received P-32 (sodium phosphate) multinational co-ordinated research project conducted by the treatment. P-32 treatment was started not earlier then 4 months IAEA. One hundred and eleven patients from 7 participating after treatment with I-131. P-32 was administered orally in 100 ml countries, with a mean age of 60 years (range: 36-81), with de of 10% glucose solution on an empty stomach, 74-120 MBq pert novo (n=47) or in-stent restenosis (n=64) and proven ischemia treatment with 4-7- day intervals. Total P-32 activity during one were included. After successful PTCA with (n=24) or without course of treatment made up 296-444 Mbq. (n=87) additional stent implantation a second standard balloon Combination radionuclide therapy with I-131 sodium iodide and was placed into the PTCA area and filled with 188Re-perrhenate. P-32 sodium phosphate was given to 4 patients with papillary and Irradiation time was 405 ± 169 sec to achieve a dose of 18 Gy at 1 follicular TC with bone metastases which did not accumulate I- mm depth from luminal surface. Six month angiographic and 131. Two of these patients had diffuse metastases to the lung clinical follow-up was available in 85 patients. Results were parenchyma. The patients received 305-369 MBq of P-32. The compared with those obtained from a control group (n=62). radiation load on the red bone marrow was 1098-1328.4 mSv at Clinical and procedural data did not differ between the groups oral P-32 administration that on the body was 823.5-996.3 mSv. except a higher rate of de novo lesions in the control group (62%) The signs of myelosuppression were not observed during the stay compared with the 188Re group (41%, p=0.0016). Binary restenosis at the Institute. One patient had insignificant reduction of rates were significantly lower at the target lesion after thrombocyte level up to 91.0 x 109 /l and leukocyte level to 2,4 õ brachytherapy compared with the control group (30% versus 109/l 2 month after the treatment. Three months after systemic 40%, p=0.049). Target vessel revascularization rate did not differ radionuclide therapy the signs of inconsiderable between both groups (8.1% versus 5.9% for the control and treated myelosuppression disappeared. group, respectively, p=0.74). Besides, late thrombosis was only Pain syndrome disappeared 5-12 days after combination systemic developed in the 188Re group (n=3), with subsequent myocardial radionuclide therapy, and the patients were able to care for infarction. An additional stent had been implanted in two of them. themselves. Flare phenomenon was not seen. A positive feature of IVRT using 188Re liquid-filled balloons is a feasible and effective combination radionuclide therapy with I-131 sodium iodide and therapeutic modality for decreasing the incidence of restenosis P-32 sodium phosphate together with treatment of bone following PTCA. Additional stenting after brachytherapy should metastases is possibility continue the treatment of metastases to be discouraged. Long term follow-up studies are needed to the sentinel lymph nodes and lung parenchyma, which often evaluate the clinical benefit of the procedure. accompany bone metastases. Observation of the patients for a year demonstrated that all the patients, which had received 112-USA combination radionuclide therapy, were alive, pain syndrome was Therapeutic Applications of Rhenium-188 in Nuclear absent in two, in two this was moderate but better then the pain Medicine and Oncology - Current Status and Expected Future before the beginning of the treatment. All patients did not Perspectives accumulate I-131 sodium iodide in the lymph nodes. Knapp Jr. F. F. (Russ) Combination systemic radionuclide therapy with I-131 sodium Nuclear Medicine Program, Isotope Development Group, Oak iodide and P-32 sodium phosphate in TC with metastases to the Ridge National Laboratory (ORNL), Oak Ridge, TN, USA bones is a method of choice and allows performing adequate treatment of the patients with a continuing process in the thyroid The increasing use of unsealed radioactive targeting agents for with metastatic involvement of the sentinel lymph nodes and lung cancer treatment requires the routine availability of cost-effective parenchyma. radioisotopes. Rhenium-188 (Re-188; half-life 16.9 hours) is a high-energy beta-emitter (Emax 2.12 MeV), readily available no- 111-URU carrier-added from the alumina-based tungsten-188 (half-life 69 Intravascular Radiation Therapy with Liquid-Filled 188Re days)/rhenium-188 generator system [1]. Rhenium-188 also Balloon Catheter: Results of an International Atomic Energy emits a 155 keV (15%) gamma photon, permitting gamma camera Agency (IAEA) Multicentre Study imaging for biodistribution and dosimetry evaluation. The Alonso O1, Chae I-H2, Chung JK2, Gutierrez C3, Kropp J4, Önsel versatile chemistry of rhenium allows attachment to a wide variety C5, Peix A6, Plonska E7, Szilvasi I8, Knapp FF9 , Padhy AK10, Storto of targeting molecules for Re-188 applications in nuclear G10, Dondi M.10 1 oncology for both palliative metastatic treatment and targeted Nuclear Medicine Centre, University of Uruguay, Montevideo; tumor therapy - radionuclide synovectomy, and coronary Uruguay, 2Seoul National University Hospital, Seoul, Republic of restenosis therapy. The long parent half-life and consistent World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 66. S-60 Abstracts: ICRT-2005 performance provide an indefinite generator shelf-life of several References months with high Re-188 elution yields (75-85 %) and consistently low W-188 parent breakthrough (< 10-6) [1]. Simple 1. Knapp FF Jr. “Rhenium-188 - A Generator-Derived post-elution concentration methods have been developed which Radioisotope for Cancer Therapy,” Cancer Biotherapy and provide very high specific volume solution of Re-188 for Radiopharm 1998; 13: 337-349 radiolabeling ( > 700 mCi/mL saline/1 Ci generator) [1]. Over 60 2. Palmedo H, Manka-Waluch A, Albers P et al. Repeated Bone physician-sponsored clinical trials are currently in progress Targeted Therapy for Hormone-Refractory Prostate worldwide with applications in nuclear medicine, nuclear Carcinoma: Randomized Phase II Trial with the New, High- oncology and interventional cardiology. Energy Radiopharmaceutical Rhenium-188-HEDP. J Clin A variety of Re-188-labeled therapeutic radiopharmaceuticals and Oncol 203; 21: 2869-2875 devices are being developed for clinical trials currently in progress 3. Liepe K, Kropp J, Runge R et al. Therapeutic Efficacy of for treatment of both benign and metastatic oncological disorders. Rhehium-188-HEDP in Human Prostate Cancer Skeletal Palliation of metastatic bone pain with Re-188-HEDP - prepared Metastases. Brit. J Cancer 2003; 89: 625-629 from a simple “kit” - has been demonstrated as a cost-effective 4. Savio E, Gaudiano J, Robles A et al. Rhenium-188-HEDP: alternative to similar agents [2-4]. Recent studies have in fact Pharmacokinetic Characterization in Osseous Metastatic demonstrated the enhancement of progression-free interval and Patients with Two Levels of Radiopharmaceutial Dose. BMC survival time by repeated Re-188-HEDP injections to patients Nucl. Med 2001; 1(23): 471-1485 with metastatic disease from prostate cancer [2]. The use of the 5. Bunjes D. 188Re-Labeled anti-CD66 Monoclonal Antibody in Re-188-labeled antiNCA95 (CD66) antibody in conjunction with Stem Cell Transplantation for Patients with High-Risk Acute external beam irradiation is an effective method for Myeloid Leukemia. Leuk Lymphoma 2002; 43: 2125-2131 myeloablation/conditioning prior to stem cell transplantation in 6. Bugaj JE, Bickel EM, Azure MT et al. Radiotherapeutic leukemia patients [5]. Rhenium-188-labeled peptides are also Efficacy of a SSTR-Targeting Peptide (188Re-P2045) in a being developed and evaluated for targeted therapy. The Re-188- Small Cell Lung Cancer (SCLC) Mouse Model. J Nucl Med P2045 SST2/SST5-binding peptide is being developed for the 2002; 43: 123P (Abstract). treatment of small cell/non small cell lung tumors and the initial 7. Paeng JC, Jeong JM, Yoon et al. Lipiodol Solution of 188Re - results of a Phase I trial have been reported [6]. HDD as a New Therapeutic Agent for Transhepatic Arterial The submitted manuscript has been authored by a contractor of the Embolization in Liver Cancer: Preclinical Study in a Rabbit U.S. Government under contract DE-AC05-00OR22725. Liver Cancer Model. J Nucl Med 2003; 44: 2033-2038 Accordingly, the U.S. Government retains a nonexclusive, 8. Duatti A, Martindale AA, Turner JH et al. Rhenium-188 royalty-free license to publish or reproduce the published form of Lipiodol Kit Formulation for Therapy of Hepatocellular this contribution, or allow others to do so, for U.S. Government Carcinoma (HCC). World J Nucl Med 2002;1: S180 purposes. 9. Sundram FX, Yu S, Somanesan S et al. Phase I Study of Therapy of refractory liver cancer is being explored by site- Transarterial Rhenium-188-HDD Lipiodol in Treatment of specific trans-arterial delivery of the Re-188-labeled HDD- [7] Inoperable Primary Hepatocellular Cacinoma - A Multicentre and DEDC-Lipiodol [8] conjugates in several countries, including Evaluation. World J. Nucl Med 2002; 1: 5-11 an IAEA-sponsored multi-center trial [9]. Use of Re-188-B20 10. Kropp J, Pinbkert J, Wunderlich G et al. Radiochemistry, albumin particles has also been reported as an effective alternative Evaluation and First Clinical Results in the Treatment of approach for the treatment of metastatic liver cancer therapy [10]. Oncologic Diseases with Rhenium-188-Labeled Although the use of radioactive stents for inhibition of restenosis Microspheres, In, Proceedings, the 11th Mediterranean following coronary angioplasty has been eclipsed at most centers Symposium on Nuclear Medicine and Radiopharmaceuticals, with the use of growth inhibitor-coated stents, the use of Re-188 Athens, Greece, May 28-30; Mediterrea Pub., Athens (ISBN liquid-filled balloons for this application has played an important 960-86437-2-4); pp. 157-166 (2003). role in developing and demonstrating the cost-effective usefulness of preventing coronary restenosis with beta-emitting 113-USA radioisotopes and still represents a cost-effective alternative for Therapy with High LET Radioisotopes: Can Sufficient restenosis therapy when cost is an issue. Levels of Attractive Auger and Alpha Emitters be Produced to The tungsten-188/rhenium-188 generator represents a convenient Make Their Use Practical ? and cost-effective system to provide high specific activity Knapp, Jr. F.F. (Rush), Mirzadeh S, Stabin M, Brill AB rhenium-188 for a wide variety of therapeutic applications. In Nuclear Medicine Program, Oak Ridge National Laboratory developing countries the tungsten-188/rhenium-188 generator is (ORNL), Oak Ridge, TN, Radiology Department, Vanderbilt of particular importance because of its indefinite useful shelf-life University, Nashville, TN, USA. and rhenium-188 represents one of the few therapeutic radioisotopes that can be cost effectively routinely available. Use Because of localized energy deposition within a very small of the tungsten-188/rhenium-188 generator in a centralized volume, cellular targeted therapy with high linear energy transfer radiopharmacy would be expected to optimize the costs for (LET) Auger-electron and alpha-particle emitting radioisotopes is broader use of Re-188 in nuclear oncology. This talk will focus of great interest. While the energy deposition from alpha particles on discussion of the clinical applications of Re-188 in nuclear usually encompasses several cell diameters, the dose from Auger oncology and the expected expanding role of this therapeutic electrons is confined to a single cell. Two major challenges for radioisotope for radionuclide therapy. broader use of Alpha and Auger emitters are the efficient and cost Acknowledgement: Research at the Oak Ridge National effective routine production of sufficient levels of these Laboratory (ORNL) supported by the U.S. Department of Energy radioisotopes, and the availability of targeting molecules to which (DOE) the under contract DE-AC05-00OR22725 with UT- the radioisotopes can be attached for cellular delivery of sufficient Battelle, LLC. levels of activity for effective therapy. Examples of several Alpha- World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 67. S-61 Abstracts: ICRT-2005 Half eV per Energy Radionuclide Life Comment Emission Transformatio Deposited s n Gram rad/mCi- x 10-2 h Accelerator produced (A)/accelerator-produced generator parent Actinium-225 10 d U-233®Th-229®Ac- a 225 Bismuth-213 45.6 From Ac-225 generator a 44.2 0.972 m Bismuth-212 60.5 From Pb-212 ???? 50.0 1.1 m Indium-111 2.8 d From Cd-111(p,n)In-111 EC 3.45 0.071 Neodynium-140 3.37 d From Pr-141(p,2n)Nd- EC 15.6 0.343 140 Reactor produced (R)/reactor-produced generator parent Platinum-195m 4.02 d From Ir-195 decay IT 18.3 0.403 Ir-193(2n,g)Ir-195 Rhodium-103m 56.1 From Ru-103 generator IT 3.7 0.081 m Ru-102(n, g)Ru-103 Table 1. Examples of High LET Radioisotope of Current Interest for Targeted Therapy Reported Production Radioisotope Yield Data Reference/Comment Actinium-225 From Th-229 decay [2] Th-229 inventory from U-233 is limited (Parent of Ra-226(p,2n)Ac-225 Bismuth-213) Yield = 9.61 mCi/mg Ra-226/h, 15.9 MeV at 50 mA current [3] Neodymium-140 Pr-141(p,2n)Nd-140 [4,5] Estimated production yield Yield = 800 mCi/mh, 35 MeV at 15 mA current Platinum-195m Ir-193(2n,g)Ir-195? Pt-195m [6,7] Initial tracer level study Ruthenium-103 Ru-102(2n,g)Ru-103m (Parent of [8] Rhodium-103m) Table 2. Production Yields of Key Examples of High LET Radioisotopes Figure 1. Reactor production of platinium-195m World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 68. S-62 Abstracts: ICRT-2005 and Auger-emitting radioisotopes of current interest are Radiochemical Separation of the Auger Electron Emitter 140 summarized in Table 1. Nd. Acta Oncologica 2000; 39: 727-730 Alpha- and Auger electron-emitting radioisotopes can be 5. Yakushev EA, Kovalik A, Filosofov DV et al. An produced in accelerators (A) and nuclear reactors (R), and Experimental Comparison of the K- and L-Auger Electron several alpha emitter congeners (i.e. thorium-229) can be Spectra Generator in the Decays of 140Nd and 111In. Appl Radiat obtained from uranium decay products. The challenge for Isot, in press (2005) reactor production, is the availability and exploitation of 6. Mirzadeh S, Du M, Beets AL, Knapp FF. High Specific methods - other then the usual radiative (n,g) production route Activity Platinum-195m,“U. S. Patent No. 6,804,319”. Issued which will provide no-carrier-added (nca) or the high specific October 12, 2004. activity radioisotopes of interest. 7. Knapp FF, Mirzadeh S, Beets AL et al. Production of The submitted manuscript has been authored by a contractor of Therapeutic Radioisotopes in the ORNL High Flux Isotope the U.S. Government under contract DE-AC05-00OR22725. Reactor for Applications in Nuclear Medicine, Oncology and Accordingly, the U.S. Government retains a nonexclusive, Interventional Cardiology, J. Radioanalyt Nuc Chem. 2005; royalty-free license to publish or reproduce the published 263 (2): 503-509 form of this contribution, or allow others to do so, for U.S. 8. Bernhardt P, Forsell-Aronsson E, Jacobsson E et al. Low Government purposes Energy Electron Emitters for targeted Therapy f Small High LET radioisotopes of current interest which are in the Tumors. Acta Oncol 2001; 40(5): 602-608 initial stages of development and/or which demonstrate 9. Mariana G, Bodel L, adelstein SJ, Kassis AI. Emerging Roles practical use in clinical trials include several alpha-emitters, in for Radiometabolic Therapy of Tumors Based on Auger particular bismuth-213 - and also the actinium-225 parent - Electron Emission. J Nucl Med 200; 41(9): 1519-1521 astatine-211 and bismuth-212. Extensive experimental studies have been reported with Auger iododeoxyuridine 114-USA (IdUR) radiolabeled with the iodine-125 emitter-labeled [1]. Future Directions in Bone-Localizing Therapeutic However, development of production and processing Radiopharmaceuticals. technologies, radiolabeling and intracellular targeting studies, Srivastava SC. Medical Department, Brookhaven National and experimental evaluation of the subsequent therapeutic Laboratory, Upton, New York, USA. potential of other Auger emitters is only in its infancy. Examples of Auger-emitters of current interest include Bone-localizing therapeutic radiopharmaceuticals are utilized on indium-111 (A), neodymium-140 (A), platinum-195m (R) the basis of the radionuclide's therapeutic particulate emissions and rhodium-103m (R production of ruthenium-103 parent) (primarily low to intermediate energy electron emission). The (Table 1). requirements therefore are different from those of bone imaging One Auger-electron emitter of particular interest is platinum- agents that consist mainly of short-lived single photon emitters. 195m [9], which has been previously available in only low Lately, the therapeutic bone-seeking radiopharmaceuticals have specific activity (approx. 1 mCi/mg). Demonstration of a new attained increasing importance due to their potential future role in indirect production route via decay of reactor-produced alleviating pain from osseous metastases in cancer patients, for the iridium-195 (Figure 2), indicates that this Auger emitter may treatment of joint pain resulting from inflamed synovium now be available in significantly higher specific activity (> 70- (radiosynovectomy) or from various forms of arthritic disease, 100 mCi/mg) which will now permit for the first time studies of and for the treatment of primary/metastatic cancer in bone. the therapeutic potential of this Auger emitter. The interest in application of radionuclides to therapy of bone Because of recent success in peptide targeting to membrane- malignancies, particularly for palliative relief of metastatic bone based cellular receptors which are often over-expressed in pain, is not new but has recently undergone a renewal. It had its tumor cells and advances in radiolabeling chemistry and origin in the earliest days of the nuclear era but fell into relative radioisotope production and processing technologies, obscurity for some time, until about two decades ago. Both Sr-89 intracellular targeted therapy with Alpha and Auger emitters and P-32 were investigated as early as the 1940's for the treatment has taken on a new dimension. This talk will review the issues of metastatic cancer to bone. Detailed investigations in the associated with the production and processing of several key seventies and eighties suggested again that Sr-89 would be useful candidates and the possibility of producing sufficient levels for relief of pain from osseous metastases, thus resulting in the required for sustained research efforts and clinical trials. FDA approval for its routine application in 1993. This work also Acknowledgement: Research at the Oak Ridge National stimulated further clinical research in order to find other b- Laboratory (ORNL) supported by the U.S. Department of emitting radionuclides, which may have improved physical Energy (DOE) the under contract DE-AC05-00OR22725 with properties that permit treatment with fewer side effects on the UT-Battelle, LLC. myeloproliferative cells in the bone marrow. The newer potential radionuclides include the FDA-approved Sm-153, and others still References undergoing investigation, e.g., Sn-117m, Lu-177, and Re- 1. Kassis AI. The Amazing World of Auger Electrons. Int. J. 186/188, etc. Radiation Biol 2004;80: 789-803 The basis for the action of most of these therapeutic agents is their 2. Boll RA, MalkemusD, Mirzadeh S. Production of incorporation into bone mineral and their beta emission, which Actinium-225 for Alpha Particle Mediated limits their range of action to the near neighborhood of their Radioimmunotherapy, Appl Radiat Isot 2005; 62: 447-679 increased concentration in pathological areas such as metastases, 3. Apostolidis C, Molinert R, McGinley et al. Cyclotron where the attempt at healing by the bone results in increased Production of Ac-225 for Targeted Alpha Therapy, Appl uptake. Tin-117m is an exception in that its emission consists Radiat Isot 2005; 62: 383-387 primarily of short-range high-LET conversion electrons rather 4. Roesch F, Brockmann J, Lebedev A et al. Production and than beta particles, thus considerably reducing the myelotoxic World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 69. S-63 Abstracts: ICRT-2005 effects in therapeutic procedures. These same radionuclides also using in vitro evolution methods. The optimized iodination have properties that make them potentially useful for the treatment procedure was as follows. NaI-131 was incubated with one of bone metastases and of many bone and joint disorders. Iodobead for 5 min in TRIS pH 6.8. The reactive iodine species This paper will briefly review and summarize the available was then separated from the bead, and the knob protein added to it chemical, biopharmacokinetic, and clinical information on the for 1 minute. This method produced I-131-knob without either current FDA-approved as well as experimental bone-localizing SDS-PAGE detectable conformational damage or loss of CAR- therapeutic radiopharmaceuticals which have so far been utilized binding activity. Following intravenous injection in mice, there primarily for bone pain palliation. Their potential usefulness for was uptake in CAR-binding tissues (liver, kidney, heart, and lung) the treatment of: 1) primary/metastatic cancer in bone; 2) joint as expected, but blood and whole body clearance were both quite pain resulting from inflamed synovium including hemophilic rapid. When mice were pre-injected with excess unlabeled knob arthropathy (radiosynovectomy); 3) rheumatoid arthritis and other (cold competitor), the level of I-131-knob (% injected dose/g) in rheumatological disorders; and 4) various osteoblastic diseases, blood was increased (19.4 vs. 2.5) with a corresponding decrease will be discussed. Because of its almost ideal therapeutic in metabolic deiodination (6.5 vs. 33.5 in stomach). properties and considerably reduced myelotoxicity, tin-117m Radioiodinated knob mutants, which are devoid of CAR-binding appears to have a distinct advantage over other radionuclides and activity showed high levels (% injected dose/g) in blood at 6 h post will be discussed in more detail. injection (31.0), whereas wild-type I-131-knob in blood at 6 h had Work supported by the United States Department of Energy decreased to background levels (2.0). Knob mutants, which are (National Nuclear Security Administration IPP Program, and the unable to interact with CAR, are retained longer in the blood and Office of Biological and Environmental Research), under have slower metabolism. These preliminary results suggest that Contract #DE-AC02-98CH10886. engineered ligands based on adenoviral sub-unit proteins (with or without the ability to bind to CAR) may prove useful as a new 115-USA class of ligands for molecular imaging and possibly for the Radiolabeled Adenoviral Sub-Unit Proteins for Molecular combined gene/radionuclide therapy of cancer. Imaging and Therapeutic Applications in Oncology. Work supported by the United States Department of Energy Suresh C. Srivastava, Medical Department, Brookhaven National (Office of Biological and Environmental Research, and the Laboratory, Upton, NE/Office of Isotope Programs), under Contract #DE-AC02- New York, USA. 98CH10886. Our group has initiated investigations on the use of radiolabeled 116-USA adenoviral (Ad) sub-unit proteins for delivering suitable Development and Evaluation of High Specific Activity radionuclides into tumor cells for molecular imaging as well as for Radioisotopes for Radiotherapy combined gene/radionuclide therapy of cancer. A number of issues C.S. Cutler, M.R. Lewis, H.P. Engelbrecht, A.R. Ketring involved in developing combined gene/radionuclide delivery into University of Missouri Research Reactor Center (MURR), tumors mediated by Ad vectors have been identified and are being Veterinary Medicine and Surgery, Columbia, MO USA addressed. Whereas current clinical trials of gene therapy using Ad vectors involve non-systemic delivery of therapeutic genes, At MU, radioisotopes are being developed and evaluated for the delivery of radionuclides preferably would involve systemic targeted radiotherapy of cancer. One approach focuses on the (i.v.) administration. The distribution and delivery of Ad sub-unit lanthanide group of radionuclides. Radiolanthanides share proteins following i.v. administration is not understood and must similar chemical properties that allow for attachment to be studied and optimized. In addition, retention of the selective biomolecules utilizing the same chelator, DOTA, but have unique binding and internalization into tumor cells of the radiolabeled half-lives (dose rates) and beta energies (tissue penetration viral vectors remains an unmet challenge. ranges). In addition they all have a low abundance gamma We used the intact adenovirus (Ad, ~80 nm diameter), native emissions that allow for imaging and tracking dosimetry. This adenoviral fiber protein (AdFP, 180 kD trimer, purified from work has resulted in the approval of Sm-153-EDTMP for the infected human cultured cells) and the adenoviral fiber “knob” palliation of pain associated with metastatic bone cancer and the protein (recombinant AdFKP, 60 kD, synthesized in E. Coli), all of investigation of Ho-166-DOTMP for marrow ablation in patients which interact with the in-vivo cellular receptor, coxsackie and suffering from multiple myeloma. Current efforts have focused adenovirus receptor (CAR) through the knob domain of the on developing high specific activity radioisotopes which can be adenovirus fiber protein. Our initial studies were aimed at attached to biomolecules that are taken up selectively by diseased optimizing the labeling conditions using I-131 and In-111 to tissues, thus delivering toxic radioactivity to diseased tissue while maintain CAR binding activity of the radiolabeled preparations. minimizing or sparing damage to healthy or normal cells. Tumor The CAR binding was retained as determined using reaction with targeting biomolecules can be radiolabeled with different biotinylated CAR followed by chemiluminescence detection. The radioisotopes tailored to treat different cancers. biodistribution results in mice and rats following i.v. Radiolabeled peptides and antibodies have shown promise for administration (autoradiography, tissue counting) showed that all radiotherapy (RIT) of cancer. However, low concentrations of three vectors localized preferentially in CAR-expressing organs tumor-associated antigens require that biomolecules be (liver, lung, heart, kidney), as expected. The CAR binding of Ad-2 radiolabeled with high specific activity radionuclides. Production wild serotype was better (~8x stronger) than Ad-12, in particular of radioisotopes by direct neutron capture often results in specific following radiolabeling. activities that are too low for RIT. Another disadvantage of the Based on the above results, we further focused on the recombinant direct approach is the production of long-lived impurities such as knob protein as well as CAR and its variable type domain CAR D1 Lu-177m (half-life = 160 days). An alternative method for for more detailed studies. The knob protein can be bioengineered producing radioisotopes is via an indirect method: neutron to interact with molecular targets, e.g., tumor-associated antigens, capture followed by beta decay of a parent radioisotope to the World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 70. S-64 Abstracts: ICRT-2005 desired daughter radionuclide. For example, neutron activation of 118-USA Nd-148 produces Nd-149 (half-life = 1.7 hr), which is followed by The role of imaging in planning therapy in cancer beta decay, producing Pm-149. Indirect methods have been Divgi C developed at MURR to produce the high specific activity Division of Nuclear Medicine, Memorial Sloan Kettering Cancer radionuclides Lu-177, Pm-149, and Ho-166. These high specific Centre, New York, activity radionuclides with differing nuclear properties have been USA attached to biomolecules and evaluated for therapeutic efficacy in tumor bearing animals. Abstract not received Isotope Half-Life Max. b Energy Ave. Range Approximate Range 119-USA (days) (MeV) (mm in water) (cell diameters) Incorporating FDG PET Imaging in the Response Criteria for Lu 6.65 0.50 0.24 20 Non-Hodgkin's Lymphoma Pm 2.21 1.1 0.71 60 Wiseman G Ho 1.12 1.8 1.38 117 Department of Radiology, Mayo Clinic, 200 First Street SW, Table 1. Nuclear Properties of Radiolanthanides. Rochester, MN 55902, USA A number of chromatographic separations have been evaluated to produce high specific activity radionuclides with mixed results. A Abstract not received variety of parameters were compared such as time of separation, efficiency of separation, ease of operation, and radionuclidic and 120-USA radiochemical purity of the desired radionuclide. In addition the Role of Radionuclides in Therapy of Haematologic radiolanthanides produced underwent a ligand titration assay to Malignancies determine percent incorporation. The radiolanthanides were then Wiseman G attached using DOTA as the chelator to biomolecules of interest. Department of Radiology, Mayo Clinic, 200 First Street SW, These radionuclides have been attached to somatostatin peptide Rochester, MN 55902, USA analogs and antibodies such as CC49 and evaluated for in vitro stability by serum and hydroxyapaptite challenge, receptor Abstract not received binding, and biodistribution in tumor bearing rodents. Although the separations have proven to be achievable they have 121-UZB at times been hindered by the introduction of stray metals Nuclear Medicine in Uzbekistan & Current status of requiring development of additional clean-up methods. Upon Radionuclide therapy in the country ICP-MS analysis separations were shown to introduce high levels Rasulova N and Khodjibekova M of Fe, Zn, Ca, Ni, Cu and P. These metals were eliminated through Department of Nuclear Medicine, Clinical Centre for Surgery, a number of techniques including prewashing the resins, removing Tashkent, Uzbekistan all metal and glass components and development of methods to remove the unwanted metals from the desired radiolanthanides. The population of Uzbekistan is 26 million and to cater to this The high specific activity radiolanthanides were complexed in population we have only two nuclear medicine departments; one high yields using the DOTA chelator (> 95% intact) and exhibited at the Clinical Centre for Surgery and the other at the Institute of high stability to both serum and hydroxyapatite challenge (bone Endocrinology, both situated in Tashkent, the capital city of mimicer) (>90% intact out to seven days). Receptor binding for Uzbekistan. Over the years through its own initiatives and through these complexes were similar and in the nanomolar range. the support provided by several International Organizations Complicated high specific activity radiolanthanides can be including the IAEA, Uzbekistan has been able to marginally produced in high radiochemical and radionuclidic purity. improve its nuclear medicine services. SPECT imaging was Furthermore, due to their similar chemistry they can be attached to introduced through generous support from IAEA in the year 2001. peptides and antibodies utilizing the DOTA chelator and As a result of this, the country is now able to provide modern in demonstrate high stability in vitro and in vivo. Biodistribution vivo nuclear medicine service to the population in a limited scale. results of these radiolanthanides attached to different targeting At the Clinical Centre for Surgery we are able to provide gamma molecules demonstrate similar in vivo distribution and illustrate camera and SPECT imaging services to patients suffering from that their therapeutic efficacy is determined largely by their half- various nephro-urological, cardiac, neuro and oncological lives (dose rates) and beta energies (tissue penetration ranges). disorders. The other nuclear medicine centre at the Institute of 117-USA Endocrinology does not have any modern imaging system. Advances in targeted radioisotope therapy in cancer However it has been engaged in providing radionuclide therapy Divgi C service for thyroid diseases like thyroid cancer and Division of Nuclear Medicine, Memorial Sloan Kettering Cancer hyperthyroidism. From the year 1983 to 1999 the country has Centre, New York, reported a total number of 6374 cases of Thyroid Cancer. This USA number is growing each year, for example the incidence of thyroid cancer in 1989 was 1.95 per 100,000, which has grown to 2.39 per Abstract not received 100,000 in 1999. While the Institute of Endocrinology provides therapeutic service to thyroid diaseases, the main role of the Nuclear Medicine Department of Republic Specialized Center of Surgery is in following-up of patients after therapy by performing large dose I-131 whole body imaging, screening for metastases and for assessment of results of radioactive iodine therapy. World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 71. S-65 Abstracts: ICRT-2005 Besides treating thyroid diseases with I-131 limited services are dose of I-131 was calculated for each patient by the following also available for treatment of polycythemia vera rubra with P-32 formula: 12 mCi x 100/24 hrs RAIU. Patients received a single and radionuclide therapy for metastatic bone pain. dose of I-131 and the range of administered I-131 dose was 825 Radiionuclide therapy is growing rapidly around the world and to- 1221 MBq. day it has become one of the most important aspect of nuclear Results revealed that 42 patients (91%) became euthyroid in three medicine practice. To this effect, there is scope for improving the months after I-131. All patients became euthyroid in 6 months. quality and quantity of radionuclide therapy service in The adenomas were reduced in size from a mean of 18.23+11.21 Uzbekistan. Various achievements, problems and requirements ml to 7.38+3.48 ml during the 12 months follow up. This was for future improvement of facilities in the country will be highly significant (p<0.05, t=3.408). The extra-nodular thyroid discussed. It is hoped that our participation in this congress will volume did not change following therapy (12.2+7.4 ml pre- provide the necessary boost to the specialty in the country and therapy vs. 11.8+7.1 ml post therapy at 12 months). incentives to the practitioners. The results of our study showed that I-131 can successfully treat not only the functional state of thyroid adenomas, but it can also 122-VEN reduce the volume of the nodules effectively. How safe is radioactive Synoviothesis? Fernando-Palazzi F, Viso R, Chakal F. Orthopaedic Unit. National Haemophilia Center. Caracas. Venezuela In order to assess the efficacy and safety of radiosynoviorthesis we performed clinical evaluation and chromosomal studies in 104 patients treated with a number of radiopharmaceuticals (61 Knees, 26 Elbows, 14 Ankles and 3 Shoulders) over a period of several years from 1976 to 1999, with a minimum follow-up period of four years. Radiopharmaceutical used were as follows: Gold Colloid (Au-198): 58 joints, Rhenium-186: 20 joints; Y-90: 26 joints. Follow-up evaluation revealed no haemarthrosis in 70% and reduced haemarthrosis in 21%, while in 6 joints there were no response (failure). Overall good results were obtained in 91%. With regard to chromosomal abnormalities, the study did not reveal any longstanding pre-malignant chromosomal abnormalities. 123-BOH Effect of radioiodine therapy on thyroid nodule size in patients with toxic adenomas Rajkovaca Z, Mijatovic J, Skrobis M, Kovacevic P Department of Nuclear Medicine, Clinical Centre Banja Luka & Department of Physiology, Medical Faculty Banja Luka, Bosnia & Herzegovina Autonomously functioning toxic adenomas are a common cause of hyperthyroidism. Surgery, radioiodine and percutaneous ethanol injection into the nodule are effective therapies. Radioiodine therapy is increasingly used as first line therapy especially in elderly patients. Radioactive iodine I-131 seems to be a good therapeutic option with low incidence of post-therapy hypothyroidism. The important therapeutic effect has also been the regression in nodule size. The aim of this study was to investigate the effect of radioiodine therapy on the size of toxic adenomas. Forty-six patients with age range of 37-76 years (Mean age=60.9 years) were followed up for a period of 12 months after I-131 therapy for toxic adenomas. Thyroid hormone levels (T3, T4 and TSH) were determined. Each patient was subjected to ultrasound and radionuclide scanning of thyroid gland at 3,6 and 12 months following I-131 therapy. Successful treatment was defined as control of hyperthyroidism and reappearance of extra-glandular thyroid tissue on Thyroid scan, which were suppressed by the hyperactive nodule prior to therapy. The volumes of the thyroid pre and post-therapy were estimated by US using the formula of ellipsoid model (ð/6 x length x width x depth). The therapeutic World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 72. S-66 Author Index Author Page No. Author Page No. Author Page No. Abdelrazek S 47 Chau T 19 Harousseau JL 29 Abtroun S 12 Chen S 19 Henni-Haddam F 12 Afanasieva NI 57,58 Chinol M 18 Hilson AJW 40 Afroz S 13 Chinwan BP 34 Hoefnagel CA 42 Ajdinovic B 52 Choudhury PS 35 Hofmann A 13 Alam F 15 Chua M 45 Horak ID 29 Aleknavicius E 41 Chung JK 59 Hossain R 17 Ali N 14 Codorean I 50 Hossain S 14,17 Ali S 14 Coudeu I 18 Huglo D 29 Allen BJ 56 Cutler CS 63 Hussain R 16 Al-Nahhas A 46,55 Dang Y 20 Islam N 14 Alonso O 59 Das BK 36,41 Islam SKM 14 Amaral H 18 Davidovic B 50 Izadian ES 37 Anand YNI 32 De la Fuente H 18 Jaksic E 51 Ang S 19,47 De Los Santos JO 22 Jankovic Z 52 Ansari S 16,37 Dewan AK 35 Jaukovic L 52 Anselmi OE 18 Dey NR 33 Jehan AH 17 Aouli S 12 Divgi C 19,41,64 Jehangir M 43 Archimandritis SC 29 Dondi M 19,59 Jeong JM 19 Artiko V 50 Dougall P 34 John P 13 Asghar S 43 Dudov A 18 Jordanou J 30 Ashok P 34 Duldulao MA 46 Joshi ND 34 Astapieva OM 58 Dumitriu L 49 Julka PK 31,34 Azra P 43 Eftekhari M 37,38 Kabir MF 15 Bal CS 31,34 Ellmann A 38,50 Kakhki VRD 7 Bandopadhyaya GP 32 Engelbrecht HP 63 Kaliska L 52 Baranauskas Z 41 Enkhtuya B 41 Karim MA 15,16,17 Barrenechea EA 19,44,45,46,47 Erdenechimeg S 19,41,42 Kasparek R 21 Basak B 33 Esfahani AF 37 Ketring AR 63 Baum RP 25,27 Fallahi B 37 Khan B 34 Bayarmaa B 42 Fard-Esfahani A 38 Khodjibekova M 64 Beatovic S 51 Farhad Ghadiri MD 38 Kirsch CM 29 Begum F 16 Fawzy A 22 Kleinman S 18 Begum R 17 Fernando-Palazzi F 65 Kling A 48 Beibutov Sh.M 13 Fettich J 53 Knapp FF 19,59,60 Beiki D 7,38 Freundschuh MP 29 Knut Liepe 24,26 Benlabgaa R 12 Galatros G 12 Kociura-Sawicka A 47 Bernal P 19 Gaston JC 46 Koeckeritz U Berzina A 39 Ghafoorian H 38 Konior M 48 Berzina D 39 Ghahremani AR 38 Kontogeorgakos D 30 Besic N 53,54 Gherghe M 49 Korol P 57 Birkenfeld B 47,48 Ghita ST 50 Korsak A 48 Botev V 18 Giannone C 12 Kostic K 50 Bouyoucef SE 12 Gil C 18 Koumarianou E 29 Bouziotis P 29 Goh A 52 Kovacevic P 65 Brecelj J 53 Goldenberg DM 29 Krishna BA 33 Brill AB 60 Goldstein A 49 Krishnakumar R 36 Budlewski T 47 Gonchigsuren D 41 Kropp J 27,29,59 Burneckis A 41 Griesinger F 29 Kulakiene I 40 Buscombe JR 19,40,55 Grmek M 53 Kumar A 19,34 Cano RA 43,44 Grushka GV 58 Kumar R 31,32 Castro M 43 Gutierrez C 59 Kuprionis G 40 Caviglia H 12 Haddad P 38 Lateiner J 29 Chae I-H 59 Hadjieva T 18 Laureta EG 46 Chakal F 65 Han R 51 Lee MC 39 Chandrashekar N 31 Hanzal A 12 Lewis MR 63 Chatal JF 29 Haque FS 17 Li J 19 World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 73. S-67 Author Index Author Page No. Author Page No. Author Page No. Limouris G 29,30 Perkins A 55,56 Snehlata 36 Lyra M 29,30 Petrovic N 50 Sohaib M 43 Majlis A 18 Phinou P 29 Solav S 30 Malhotra A 31,32,34,36,41 Plonska E 59 Soldner J 25 Malhotra G 41 Poksi A 23 Sood A 35 Mansouri B 1 Postigo J 44 Sopotyk A 47 Marinescu G 50 Pourbeigi H 38 Soroa V 12 Markovic S 51 Pradhan PK 36,41 Srivastava D 19 Martinez F 44 Pruzzo R 18 Srivastava SC 62 Maulik SK 32 Pucar D 52 Stabin M 60 Mazilu C 50 Pusuwan P 19 Staudenherz A 13 Meigooni AS 38 Quilieva AO 13 Storto G 59 Meller J 29 Rahman HA 15,16 Strauß H-J 25 Mendoza G 43,44 Rahman MS 1 6 Sundram FX 19,41,52 Miah SH 15 Rahman MU 17 Szilvasi I 59 Mijatovic J 65 Rahman SH 16 Szumowski P 47 Mikalauskas V 40 Rajini TR 32 Taghizadeh-asl M 38 Mikolajczak R 48 Rajkovaca Z 65 Takavar A 38 Mirzadeh S 60 Rashid H 14 Tanada S 38 Mishra SK 36 Rasulova N 64 Tiskevicius S 41 Missailidis S 55 Rath GK 34 Torres F 44 Mititelu MR 50 Ray S 33 Tripathi M 31,36 Mitsokapas N 29 Reyes C 18 Tsevelmaa L 42 Mohanty BN 36 Reynen K Turner JH 12 Momta S 17 Reznak I 21 Vajauskas D 40 Morales B 18 Rimbu A 50 Varas M 18 Morales R 43,44 Rogowski F 47 Varma IK 32 Morschhauser F 29 Rojas A 18 Varvarigou AD 29 Mushtaq A Rossi R 18 Vasiliev L Ya 57 Muthu GS 32 Roznere L 39 Velazquez Espeche MH 12 Muzhychuk OV 58 Saavedra P 44 Vereb M 52 Nair O 34 Saesow N 55 Vevere I 39 Nanayakkara D 54 Saghari M 37 Vidergar-Kralj B 54 Nasirova FJ 13 Salas A 44 Vilchez C Naumann R 29 Samarina G 23 Vinjamuri S 57 Navarra S 45 San Luis TOL 47 Viso R 65 Nazarenko S 23 Sanchez P Vlahos L 30 Neves M 48 Sankar R 32 Vlajkovic M 50 Nicolini JO 12 Santiago J 45 Vogel C 18 Nisa L 16,17 Sarika 34 Warbey VS 40 Obaldo J 46 SasakiY 38 Watanabe N 38 Obradovic V 50 Saw MM 52 Wegener WA 29 Ogbac R 47 Schaffarich MP 13 Wehrmann C 27 Oliveira A 48 Schwarzbartl-Pevec A 53,54 Wiseman G 64 Ong A 44,45 Seam RK 35 Xanthopoulos S 29 Onkhuudai P 19,41 Sellah M 1 Yasmin S 17 Onsel C 59 Seminario C 43 Yousuf M 43 Otakar Kraft 20,21 Senftleben S 27 Zagar I 53,54 Padhy AK 19,41,46,59 Senthamizhchelvan S 34 Zelek Z 48 Paganelli G 18 Senthilnathan MS 41 Zhang W 19 Pandey D 34 Sergieva S 18 Zheng R 19 Pant GS 34 Shahidullah M 14 Zikos C 29 Papanikolos G 29,30 Sharma SK 33 Zuchlinska M 48 Parfienczyk A Shiraliyev OK 13 Paul AK 15,16 Shukla J 32 Pawlak D 48 Sinzinger H 13 Peix A 59 Skrobis M 65 World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 74. 10th COLOMBIAN CONGRESS OF NUCLEAR MEDICINE Third Announcement: You are most welcome to participate in the 10th auditoria where all the lectures, scientific Colombian Congress of Nuclear Medicine, sessions and business meetings will be held. The scheduled to be held at Bucaramanga, main economic activity of the area is trading in Colombia, from November 4 to 6, 2005. footwear and garments. Their gastronomy is Bucaramanga is a beautiful city close to Bogotá recognized by the delicious variety of meat and (30 minutes by plane), located at 1000 meters the typical corn bread called: ¨arepa¨. above sea level. The venue of the congress will be ¨Palonegro¨, South of the city, 15 minutes by For further information please contact: road from downtown and 30 minutes from the Dr. Leonardo Cadavid: cadavidl@hotmail.com airport. It is a paradise resort with several ,President. sporting facilities: golf field, swimming pools, Dr. Patricia Bernal: patbernal@unete.com, tennis and a hotel with comfortable rooms and scientific committee World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005
  • 75. AOTA Meeting in Philippines FIRST ANNOUNCEMENT: D ROI ASSO 8th Asia Oceania Thyroid HY CI T Association Congress ATI IPPINE February 4-6, 2007 ON, INC PHIL . 19 64 ASIA & OCEANIA THYROID ASSOCIATION Organizing Committee: Secretariat: Venue: Advisor: St Lukes Medical Center Westin Philippine Dr Teofilo San Luis 10th Floor, Room No. 1002 Plaza Hotel, Manila Chairman: South Tower Cathedral Heights Bldg Dr. L. Mercado-Asis E. Rodriguez Sr Avenue Chairman, Scientific Committee: Quezon City 1102 Dr. E. Barrenechea Tele-fax: 00-63-2-7252133, 7230101, 9252891 Attention: Dr. E. Barrenechea emieab@yahoo.com European Thyroid Association A M E R I C A N T H Y R O I D ETA LATIN AMERICAN A S S O C I AT I O N THYROID SOCIETY F O U N D E D 1 9 2 3 World Journal of Nuclear Medicine, Volume 4, Number 3, July 2005