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  1. 1. January 15 Expertise of the VUmc Department of Nuclear Medicine & PET Research and the BV Cyclotron VU, Amsterdam The Department of Nuclear Medicine & PET Research of the VU University Medical Centre (VUmc), together with the BV Cyclotron VU, provides a means to fully develop radiopharmaceuticals for PET and SPECT in both animal and human studies. Expertise ranges from radionuclide production, through new tracer development and preclinical evaluation, to clinical use of new and existing tracers with highly qualified specialists who operate in a truly multidisciplinary environment. The whole process can be performed according to state-of-the-art GMP/GLP/GCP standards. In addition, the departmental radiopharmaceutical research, development and production site (Radionuclide Centre: RNC) was recently inspected by the Dutch Health Care Inspectorate and is licensed to manufacture tracers for human use according to the latest EU guidelines. This position paper provides an overview of current expertise, noting that developments are ongoing. Contact Prof. dr. A.A. Lammertsma Department of Nuclear Medicine & PET research VU University Medical Centre De Boelelaan 1115 1081 HV Amsterdam The Netherlands +31-20-4444214 +31-20-4443090 1
  2. 2. Overview of available tracers Licensed PET radiopharmaceuticals: 11 C labelled: flumazenil, PK11195, raclopride, verapamil, R116301, palmitate, R107474, DASB, PIB 18 F labelled: FDG, FLT, fluoride, FP-β-CIT, MPPF, FDDNP,proline 15 O labelled: H2O, O2,, CO, CO2 In development: 11 C labelled: docetaxel, WAY100635,deprenyl, methionine 13 N labelled: N2 18 F labelled: FAZA, fluoromethylcholine Licensed SPECT radiopharmaceuticals: 123 I labelled: R91150, iomazenil, hippuran, iodine, MIBG, β-CIT 81m Kr: Generator Monoclonal antibodies and peptides Validated and universal procedures are in place for labeling antibodies and peptides for pharmacokinetics/biodistribution studies (99m Tc, 186 Re, 123 I, 125 I, 131 I, 111 In, 177 Lu), SPECT imaging (99m Tc, 186 Re, 123 I, 131 I, 111 In, 177 Lu), PET imaging (68 Ga, 89 Zr, 124 I) and radioimmunotherapy (186 Re, 131 I, 177 Lu, 90 Y). In recent years more than 15 different radioimmunoconjugates have been produced for clinical evaluation, either in house or at other institutes. Several R&D collaborations with biotech companies are ongoing. All quality tests are in place: radiochemical purity, conjugate stability, substitution ratio, antibody integrity, immunoreactivity, preclinical in vivo behavior, sterility, pyrogenicity and immunogenicity. Isotopes available from Cyclotron production: 11 C, 15 O, 18 F, 123 I,124 I, 88 Zr, 89 Zr, 81 Rb/81m Kr Collaborations The department collaborates with several research centres and opinion leaders in the field of molecular imaging. The department is a preferred centre for Boehringer Ingelheim, Tyco/Mallinckrodt, Johnson & Johnson, IBA Molecular, Schering, Philips, Ablynx, Aventis, Macrocyclics and Novartis for, amongst others, the development and application of molecular imaging. These cover the whole range of collaboration possibilities, from a custom radiolabelling service to an interactive collaborative approach to development of methodology. Overview of available tracer kinetic models and data analysis procedures General models and data analysis tools Single tissue, two tissue (reversible and irreversible), reference tissue (Lammertsma), steady state (Jones, Lammertsma) and linearised (Patlak, Logan, Blomqvist, Ichise) models, spectral (Cunningham), cluster (Ashburner) and factor (Hermansen) analysis, basis pursuit (Gunn), parametric imaging (linearisations, basis functions), metabolite models, dose ranging studies, biological half-life studies Tracer kinetic models for specific applications 2
  3. 3. Perfusion, perfusable tissue index, glucose metabolism, oxygen utilisation, fatty acid metabolism, blood volume, haematocrit, integrity blood-brain barrier, P-glycoprotein function, pH, osteoblast activity, TK1 activity, MAO-B activity, dopamine D2 and D1 receptors, dopamine transporters, central (GABAA) and peripheral benzodiazepine receptors, serotonin 5-HT1A receptors, NK1 receptors Overview of available methodologies and animal models Methodologies Several in vitro, in vivo and ex vivo techniques such as autoradiography, binding studies, cell cultures, molecular biology techniques, FACScan analysis, enzyme assays, (pretreated) biodistribution studies, animal PET, anesthaesia (both inhalation and injection) Animal species Rats, mice, rabbits, minipigs, rhesus monkeys, transgenic mice, nude mice and rats Animal models Oncology: breast, cervical, head & neck, lung, prostate and colon cancer, glioma Neurology: Parkinson’s disease, depression, neurotrauma, MS, epilepsy Cardiology: minipigs Other: osteomyelitis Overview of clinical studies General Medical technology assessment (MTA), PET in drug development Neurology Alzheimer’s and Parkinson’s disease, Epilepsy Psychiatry Anxiety & depression, Schizophrenia, Post traumatic stress disorder Cardiology Myocardial ischemia, Heart failure Oncology (only main studies) Lung, breast and head & neck cancer, response monitoring (chemotherapy & radiotherapy) 3
  4. 4. Staff and facilities BV Cyclotron VU Philips AVF 30 cyclotron 2 IBA 18/9 cyclotrons Fully equipped GMP hotlab for the commercial production of [18 F]FDG, 81m Kr and [123 I] labelled products Staff P.J. van der Jagt, PhD, General manager P.J. van Leuffen, Head production R. Mooij, Head cyclotron operations P.S. Kruijer, BSc, Head commercial production radiopharmaceuticals F. van Langevelde, PhD, Head isotope production research Department of Nuclear Medicine & PET Research State-of-the-art whole body PET camera (HR+, CTI/Siemens) High resolution research PET camera (HRRT, CTI/Siemens) Time-of-flight PET/CT scanner to be installed November 2006 Dedicated rodent PET scanner to be installed Spring 2007 Medrad infusion system (controlled injections/infusions) Veenstra on-line blood withdrawal & detection systems Beta-probe RDS111 cyclotron (CTI) Oxygen-15 gas delivery system 25 Separate type II labs for working with radioactive material GMP compliant hotlab with 6 hotcells 3 research hotcells, 1 shielded fumehood Metabolite analysis lab Small animal housing facilities Multiple HPLC and GC systems Multiple gammacounters and betacounters Phosphor imager Staff Heads of Department Prof. O.S. Hoekstra, MD, PhD, clinical Prof. A.A. Lammertsma, PhD, research PET Chemistry A.D. Windhorst, PhD D. Laan, BSc M.P.J. Mooijer, BSc P.J. Klein, BSc R.P. Klok, BSc A.Y. Rijnders, BSc R. van Kooij, BSc J.S. Schepers, BSc Iodine chemistry (SPECT) 4
  5. 5. J.D.M. Herscheid, PhD J.L.H. Eersels, MSc J. Verbeek, BSc Monoclonal antibody labelling Prof. G.A.M.S. van Dongen, PhD G.W.M. Visser, PhD Metabolite analysis G. Luurtsema, PhD H.N.J.M. Greuter, BSc R.C. Schuit, BSc K. Takkenkamp, BSc P. van Ophemert, BSc Biology C.F.M. Molthoff, PhD A.A. Geldof, PhD N. Proost, BSc Pharmacy, QA/QC N.H. Hendrikse, PharmD, PhD R.P. Klok, BSc Physics A. van Lingen, PhD R. Boellaard, PhD M. Lubberink, PhD R. Kloet, BSc Nuclear medicine E.F.I. Comans, MD, PhD B.N.M. van Berckel, MD, PhD P.Raijmakers, MD, PhD A van Schie, MD Instrumentation L.F. van Rooij F.P. Buijs J.F. Keus A. de Nooijer P. Schollema R.P. van der Valk Health Physics A. van Lingen, PhD J. Boesten M. Wiegman T. Weijer Administration N. Bock A. Kroonenberg-Kalwij J. van der Kuij G. Stolker-Bouknecht Above list of staff excludes temporary staff employed on various grants. In addition, some 30 to 40 PhD students perform their PhD research in the Department of Nuclear 5
  6. 6. Medicine & PET Research. Most clinical research studies are performed in close collaboration with the respective clinical departments of the VUmc. 6
  7. 7. Recent publications (PET only; from 2004 onwards) Airaksinen AJ, Jablonowski JA, van der Mey M, Barbier AJ, Klok RP, Verbeek J, Schuit R, Herscheid JDM, Leysen JE, Carruthers NI, Lammertsma AA, Windhorst AD (in press) Radiosynthesis and biodistribution of a histamine H3-receptor antagonist 4-[3-(4-piperidin-1-yl-but-1-ynyl)-[11 C]benzyl]- morpholine: evaluation of a potential PET ligand. Nucl Med Biol. Annema JT, Hoekstra OS, Smit EF, Veselic M, Versteegh MI, Rabe KF (2004) Towards a minimally invasive staging strategy in NSCLC: analysis of PET positive mediastinal lesions by EUS-FNA. Lung Cancer 44: 53-60. Arwert LI, Veltman DJ, Deijen JB, Lammertsma AA, Jonker C, Drent ML (2005) Cognitive functioning and the growth hormone/insuline-like growth factor-I (GH/IGF-I) axis in elderly subjects: a positron emission tomography study. Neuroendocrinology 81: 31-40. Bax JJ, Beanlands RS, Klocke FJ, Knuuti J, Lammertsma AA, Schaefers MA, Schelbert HR, Von Schulthess GK, Shaw LJ, Yang GZ, Camici PG (in press) Diagnostic and clinical perspectives of fusion imaging in cardiology: Is the total greater than the sum of its parts? Heart. Bipat S, van Leeuwen MS, Comans EF, Pijl ME, Bossuyt PM, Zwinderman AH, Stoker J (2005) Colorectal liver metastases: CT, MR imaging, and PET for diagnosis--meta-analysis. Radiology 237: 123-131. Blok BFM, Groen J, Bosch JLHR, Veltman DJ, Lammertsma AA (in press) Different brain effects during chronic and acute sacral neuromodulation in urge incontinent patients with implanted neuromostimulators. Br J Urol. Boellaard R, Knaapen P, Rijbroek B, Luurtsema G, Lammertsma AA (2005) Evaluation of basis function and linear least squares methods for generating parametric blood flow images using 15 O-water and PET. Mol Im Biol 7: 273-285. Boellaard R, Krak NC, Hoekstra OS, Lammertsma AA (2004) Effects of noise, image resolution and ROI definition on the accuracy of standard uptake values: a simulation study. J Nucl Med 45: 1519- 1527. Boellaard R, van Lingen A, van Balen SCM, Lammertsma AA (2004) Optimization of attenuation correction for positron emission tomography studies of thorax and pelvis using count-based transmission scans. Phys Med Biol 49: N31-N38. Börjesson PKE, Jauw YWS, Boellaard R, de Bree R, Comans EFI, Roos JC, Castelijns JA, Vosjan MJWD, Kummer JA, Leemans CR, Lammertsma AA, Van Dongen GAMS (2006) Performance of immuno-positron emission tomography with zirconium-89-labeled chimeric monoclonal antibody U36 in the detection of lymph node metastases in head and neck cancer patients. Clin Cancer Res 12: 2133- 2140. Borst GR, Belderbos JSA, Boellaard R, Comans EFI, de Jaeger KD, Lammertsma AA, Lebesque JV (2005) Standardized FDG uptake: a prognostic factor for inoperable non-small cell lung cancer. Eur J Canc 41: 1533-1541. Brouwer J, de Bree R, Comans EF, Castelijns JA, Hoekstra OS, Leemans CR (2004) 18 FDG PET in the clinically negative neck: is it likely to be superior? Eur Arch Otorhinolaryngol 261: 479-483. Brouwer J, de Bree R, Hoekstra OS, Golding RP, Langendijk JA, Castelijns JA, Leemans CR (2005) Screening for distant metastases in patients with head and neck cancer: is chest computed tomography sufficient? Laryngoscope 115: 1813-1817. Brouwer J, de Bree R, Hoekstra OS, Langendijk JA, Castelijns JA, Leemans CR (2005) Screening for distant metastases in patients with head and neck cancer: what is the current clinical practice? Clin Otolaryngol 30: 438-443. 7
  8. 8. Brouwer J, Bodar EJ, de Bree R, Langendijk JA, Castelijns JA, Hoekstra OS, Leemans CR (2004) Detecting recurrent laryngeal carcinoma after radiotherapy: room for improvement. Eur Arch Otorhinolaryngol 261: 417-422. Dijkmans PA, Knaapen P, Aiazian E, Visser CA, Lammertsma AA, Visser FC, Kamp O (2006) Quantification of myocardial perfusion using intravenous myocardial contrast echocardiography in healthy volunteers: comparison with positron emission tomography. J Am Soc Echocardiogr 19: 285- 293 Eersels JLH, Travis MJ, Herscheid JDM (2005) Manufacturing I-123 labelled radiopharmaceuticals. Pitfalls and solutions. J Label Compd Radiopharm 48: 241-257. Greuter HNJM, van Ophemert PLB, Luurtsema G, van Berckel BNM, Franssen EJF, Windhorst BD, Lammertsma AA (2005) Optimizing an on-line SPE-HPLC method for analysis of [11 C]1-(2- chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide [(R)-PK11195] and its metabolites in man. Nucl Med Biol 32: 307-312. Greuter HNJM, van Ophemert PLB, Luurtsema G, Franssen EJF, Boellaard R, Lammertsma AA (2004) Validation of a multiwell γ-counter for measuring high-pressure liquid chromatography metabolite profiles. J Nucl Med Technol 32: 28-32. Herder GJ, Golding RP, Hoekstra OS, Comans EF, Teule GJ, Postmus PE, Smit EF (2004) The performance of (18)F-fluorodeoxyglucose positron emission tomography in small solitary pulmonary nodules. Eur J Nucl Med Mol Imaging 31: 1231-1236. Herder GJ, van Tinteren H, Golding RP, Kostense PJ, Comans EF, Smit EF, Hoekstra OS (2005) Clinical prediction model to characterize pulmonary nodules: validation and added value of 18 F- fluorodeoxyglucose positron emission tomography. Chest 128: 2490-2496. Van den Heuvel OA, Veltman DJ, Groenewegen HJ, Dolan RJ, Cath DC, Boellaard R, Mesina CT, van Balkom AJLM, van Oppen P, Witter MP, Lammertsma AA, van Dyck R (2004) Amygdala activity in obsessive-compulsive disorder with contamination fear: a study with oxygen-15 water positron emission tomography. Psychiatry Res 132: 225-237. Hoekstra CJ, Stroobants SG, Smit EF, Vansteenkiste J, van Tinteren H, Postmus PE, Golding RP, Biesma B, Schramel FJHM, van Zandwijk N, Lammertsma AA, Hoekstra OS (2005) Prognostic relevance of response evaluation using [18 F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in patients with locally advanced non-small-cell lung cancer. J Clin Oncol 23: 8362-8370. Van der Hoeven JJM, Krak NC, Hoekstra OS, Comans EFI, Boom RPA, van Geldere D, Meijer S, van der Wall E, Buter J, Pinedo HM, Teule GJJ, Lammertsma AA (2004) 18 F-2-fluoro-2-deoxy-D-glucose positron emission tomography in staging of locally advanced breast cancer. J Clin Oncol 22: 1253- 1259. Hofman HA, Knaapen P, Boellaard R, Bondarenko O, Götte MJW, van Dockum WG, Visser CA, van Rossum AC, LammertsmaAA, Visser FC (2005) Measurement of left ventricular volumes and function with O-15-labeled carbon monoxide gated positron emission tomography: comparison with magnetic resonance imaging. J Nucl Cardiol 12: 639-644. Hooft L, van der Veldt AA, van Diest PJ, Hoekstra OS, Berkhof J, Teule GJ, Molthoff CF (2005) [18 F]fluorodeoxyglucose uptake in recurrent thyroid cancer is related to hexokinase I expression in the primary tumor. J Clin Endocrinol Metab 90: 328-334. Hwang D, Narendran R, Huang Y, Slifstein M, Talbot P, Sudo Y, van Berckel BNM, Kegeles LS, Martinez D, Laruelle M (2004) Quantitative analysis of N-[11 C]propyl-norapomorphine ([11 C]NPA) in vivo binding in nonhuman primates. J Nucl Med 45: 338-346. 8
  9. 9. De Jong HWAM, Boellaard R, Lenox M, Michel C, Lammertsma AA (2004) Correction for emission contamination in transmission scans for the High Resolution Research Tomograph. IEEE Trans Nucl Sci 51: 673-676. Joshi U, Hoekstra OS, Boellaard R, Comans EF, Raijmakers PG, Pijpers RJ, Miller SD, Teule GJ, van Lingen A (2004) Initial experience with a prototype dual-crystal (LSO/NaI) dual-head coincidence camera in oncology. Eur J Nucl Med Mol Imaging 31: 596-8. Joshi U, van der Hoeven JJ, Comans EF, Herder GJ, Teule GJ, Hoekstra OS (2004) In search of an unknown primary tumour presenting with extracervical metastases: the diagnostic performance of FDG-PET. Br J Radiol 77: 1000-1006. Joshi U, Raijmakers PG, van Lingen A, Comans EF, Pijpers R, Teule GJ, Hoekstra OS (2005) Evaluation of pulmonary nodules: comparison of a prototype dual crystal (LSO/NAI) dual head coincidence camera and full ring positron emission tomography (PET). Eur J Radiol 55: 250-254. Klok RP, Klein PJ, Herscheid JDM, Windhorst AD (2006) High yielding and GMP compliant synthesis of the dopamine transporter ligand FP-β-CIT. J Label Compd Radiopharm 49: 77-89. Klok RP, Windhorst AD (in press) A general GC analysis method for the determination of residual solvents in PET tracer formulations. Nucl Med Biol. Knaapen P, Boellaard R, Götte MJW, Dijkmans PA, van Campen LMC, de Cock CC, Luurtsema G, Visser CA, Lammertsma AA, Visser FC (2004) Perfusable tissue index as a potential marker of fibrosis in patients with idiopathic dilated cardiomyopathy. J Nucl Med 45: 1299-1304. Knaapen P, van Campen LM, de Cock CC, Götte MJ, Visser CA, Lammertsma AA, Visser FC (2004) Effects of cardiac resynchronization therapy on myocardial perfusion reserve. Circulation 110: 646- 651. Knaapen P, van Dockum WG, Bondarenko O, Kok WEM, Götte MJW, Boellaard R, Beek AM, Visser CA, van Rossum AC, Lammertsma AA, Visser FC (2005) Delayed contrast enhancement and perfusable tissue index in hypertrophic cardiomyopathy: comparison between cardiac MRI and PET. J Nucl Med 46: 923-929. Knaapen P, Lammertsma AA, Visser FC (2005) Enhancement of perfusion reserve by cardiac resynchronization therapy. Eur Heart J 26: 1447-1448. Knaapen P, Bondarenko O, Beek AM, Götte MJW, Boellaard R, van der Weerdt AP, Visser CA, van Rossum AC, Lammertsma AA, Visser FC (2006) Impact of scar on water-perfusable tissue index in chronic ischemic heart disease: evaluation with PET and contrast-enhanced MRI. Mol Im Biol 8: 245- 251. Knaapen P, Götte MJW, Paulus WJ, Zwanenburg JJM, Dijkmans PA, Boellaard R, Marcus JT, Twisk JWR, Visser CA, van Rossum AC, Lammertsma AA, Visser FC (2006) Does myocardial fibrosis hinder contractile function and perfusion in idiopathic dilated cardiomyopathy? PET and MRI imaging study. Radiology 240: 380-388. Krak NC, Boellaard R, Hoekstra OS, Twisk JWR, Hoekstra CJ, Lammertsma AA (2005) Effects of ROI definition and reconstruction method on quantitative outcome and applicability in a response monitoring trial. Eur J Nucl Med Mol Imaging 32: 294-301. Krak NC, Hoekstra OS, Lammertsma AA (2004) Measuring response to chemotherapy in locally advanced breast cancer: methodological considerations. Eur J Nucl Med Mol Imaging 31: S103-S111. Kropholler MA, Boellaard R, Schuitemaker A, van Berckel BNM, Luurtsema G, Windhorst AD, Lammertsma AA (2005) Development of a tracer kinetic plasma input model for (R)-[11 C]PK11195 brain studies. J Cereb Blood Flow Metab 25: 842-851. 9
  10. 10. Kropholler MA, Boellaard R, Schuitemaker A, Folkersma H, van Berckel BNM, Lammertsma AA (in press) Evaluation of reference tissue models for the analysis of [11 C](R)-PK11195 studies. J Cereb Blood Flow Metab. Lammertsma AA, Hoekstra CJ, Giaccone G, Hoekstra OS (2006) How should we analyse FDG PET studies for monitoring tumour response? Eur J Nucl Med Mol Imaging 33, Suppl 1: S16-S21. Liefaard LC, Ploeger BA, Molthoff CFM, Boellaard R, Lammertsma AA, Danhof M, Voskuyl RA (2005) Population pharmacokinetic analysis for simultaneous determination of Bmax and KD in vivo by positron emission tomography. Mol Im Biol 7: 411-421. Luurtsema G, de Lange ECM, Lammertsma AA, Franssen EJF (2004) Transport across the blood-brain barrier: stereoselectivity and PET-tracers. Mol Im Biol 6: 306-318. Luurtsema G, Molthoff CFM, Schuit RC, Windhorst AD, Lammertsma AA, Franssen EJF (2005) Evaluation of (R)-[11 C]verapamil as PET tracer of P-glycoprotein function in the blood-brain barrier: kinetics and metabolism in the rat. Nucl Med Biol 32: 87-93. Lubberink M, Boellaard R, van der Weerdt AP, Visser FC, Lammertsma AA (2004) Quantitative comparison of analytic and iterative reconstruction methods in 2- and 3-dimensional dynamic cardiac 18 F-FDG PET. J Nucl Med 45: 2008-2015. Lubberink M, Luurtsema G, van Berckel BNM, Boellaard R, Toornvliet JR, Windhorst AD, Franssen EJF, Lammertsma AA (in press) Evaluation of a tracer kinetic models for quantification of P- glycoprotein function using (R)-[11 C]verapamil and PET. J Cereb Blood Flow Metabol. Van der Meij M, Janssen CG, Janssens FE, Jurzak M, Langlois X, Sommen FM, Verreet B, Windhorst AD, Leysen JE, Herscheid JDM (2005) Synthesis and biodistribution of [11 C]R116301, a promising PET ligand for central NK1 receptors. Bioorg Med Chem 13: 1579–1586. Van der Meij M, Windhorst AD, Kennis L, Bisschof F, Klok RP, Bakker M, Langlois X, Heylen L, Herscheid JDM, Jurzak M, Leysen JE (2006) Synthesis and in vivo studies of [11 C]R107474, a new radiolabeled α2-adrenoceptor antagonist. Bioorg Med Chem 14: 4526-4543. Mijnhout GS, Riphagen II, Hoekstra OS (2004) Update of the FDG PET search strategy. Nucl Med Commun 25: 1187-1189. Moll AC, Hoekstra OS, Imhof SM, Comans EF, Schouten-van Meeteren AY, van der Valk P, Boers M (2004) Fluorine-18 fluorodeoxyglucose positron emission tomography (PET) to detect vital retinoblastoma in the eye: preliminary experience. Ophthalmic Genet 25: 31-35. Nestor M, Persson M, van Dongen GAMS, Jensen HJ, Lundqvist H, Anniko M, Tolmachev V (2005) In vitro evaluation of the astatinated chimeric monoclonal antibody U36, a potential candidate for treatment of head and neck squamous cell carcinoma. Eur J Nucl Med Mol Imaging 32: 1296-1304. Noske DP, Peerdeman SM, Comans EF, Dirven CM, Knol DL, Girbes AR, Vandertop WP (2005) Cerebral microdialysis and positron emission tomography after surgery for aneurysmal subarachnoid hemorrhage in grade I patients. Surg Neurol 64: 109-115. Van Oost FJ, van der Hoeven JJ, Hoekstra OS, Voogd AC, Coebergh JW, Van De Poll-Franse LV (2004) Staging in patients with locoregionally recurrent breast cancer: current practice and prospects for PET. Eur J Cancer 40: 1545-1553. Pasic A, Brokx HA, Comans EF, Herder GJ, Risse EK, Hoekstra OS, Postmus PE, Sutedja TG (2005) Detection and staging of preinvasive lesions and occult lung cancer in the central airways with 18 F- fluorodeoxyglucose positron emission tomography: a pilot study. Clin Cancer Res 11: 6186-6189. Perk LR, Visser GWM, Vosjan MJWD, Stigter-van Walsum M, Tijink BM, Leemans CR, van Dongen GAMS (2005) Evaluation of 89 Zr as a PET surrogate radioisotope for scouting the biodistribution of the 10
  11. 11. therapeutic radiometals 90 Y and 177 Lu in tumor bearing nude mice, after coupling to the internalizing antibody cetuximab. J Nucl Med 46: 1998-1906. Perk LR, Visser OJ, Stigter-van Walsum M, Vosjan MJWD, Visser GWM, Zijlstra JM, Huijgens PC, van Dongen GAMS (in press) Preparation and evaluation of 89 Zr-Zevalin for monitoring 90 Y-Zevalin biodistribution with positron emission tomography. Eur J Nucl Med Mol Imaging. Van Rij CM, Huitema ADR, Swart EL, Greuter HNJM, Lammertsma AA, van Loenen AC, Franssen EJF (2005) Population plasma pharmacokinetics of 11 C-flumazenil at tracer concentrations. Br J Clin Pharmacol 60: 477-485. Rimoldi O, Schäfers KP, Boellaard R, Turkheimer F, Stegger L, Law MP, Lammertsma AA, Camici PG (2006) Quantification of subendocardial and subepicardial blood flow using 15 O-labeled water and PET: experimental validation. J Nucl Med. 47: 163-172. Shankar LK, Hoffman JM, Bacharach S, Graham MM, Karp J, Lammertsma AA, Larson S, Mankoff DA, Siegel BA, van den Abbeele A, Yap J, Sullivan D (2006) Consensus recommendations for the use of 18 F-FDG as an indicator of therapeutic response in patients in national cancer institute trials. J Nucl Med 47: 1059-1066. Steenbakkers RJ, Duppen JC, Fitton I, Deurloo KE, Zijp LJ, Comans EF, Uitterhoeve AL, Rodrigus PT, Kramer GW, Bussink J, De Jaeger K, Belderbos JS, Nowak PJ, van Herk M, Rasch CR (2006) Reduction of observer variation using matched CT-PET for lung cancer delineation: a three- dimensional analysis. Int J Radiat Oncol Biol Phys 64: 435-448. Sturkenboom M, Franssen E, Berkhof J, Hoekstra OS (2004) Physiological uptake of 18FDG uptake in the neck and upper chest region: are there predictive characteristics? Nucl Med Commun 25: 1109- 1112. Tijink BM, Neri D, Leemans CR, Budde M, Berndorff D, Stigter-van Walsum M, Zardi L, van Dongen GAMS (2006) Radioimmunotherapy of head and neck cancer xenografts using 131 I-labeled antibody L19-SIP for selective targeting of tumor vasculature. J Nucl Med 47: 1127-1135. Toornvliet R, van Berckel BNM, Luurtsema G, Lubberink M, Geldof AA, Bosch TM, Oerlemans R, Lammertsma AA, Franssen EJF (2006) Effect of age on functional P-glycoprotein in the blood brain barrier measured using (R)- [11 C]verapamil and positron emission tomography. Clin Pharmacol Ther 79: 540-548. Van Tilburg EW, Franssen EJF, van der Hoeven JJM, van der Meij M, Elshove D, Lammertsma AA, Windhorst AD (2004) Radiosynthesis of [11 C]docetaxel. J Label Compd Radiopharm 47: 763-777. Van Tilburg E, Windhorst AD, van der Meij M, Herscheid JDM (2006) One-pot synthesis of [11 C]ureas via triphenylphosphinimines. J Label Compd Radiopharm 49: 321-330. Veltman DJ, Tuinebreijer WF, Winkelman D, Lammertsma AA, Witter MP, Dolan RJ, Emmelkamp PMG (2004) Neurophysiological correlates of habituation during exposure in spider phobia. Psychiatry Res 132: 149-158. Verel I, Visser GW, Vosjan MJ, Finn R, Boellaard R, van Dongen GA (2004) High-quality 124 I-labelled monoclonal antibodies for use as PET scouting agents prior to 131 I-radioimmunotherapy. Eur J Nucl Med Mol Imaging 31: 1645-1652. Verel I, Visser GWM, van Dongen GAMS (2005) The promise of immuno-PET in radioimmunotherapy. J Nucl Med 46: 164S-171S. Van der Weerdt AP, Boellaard R, Knaapen P, Visser CA, Lammertsma AA, Visser FC (2004) Post- injection transmission scanning in myocardial 18F-FDG PET studies using both filtered backprojection and iterative reconstruction. J Nucl Med 45: 169-175. 11
  12. 12. Westerterp M, van Westreenen HL, Reitsma JB, Hoekstra OS, Stoker J, Fockens P, Jager PL, Eck-Smit BL, Plukker JT, van Lanschot JJ, Sloof GW (2005) Esophageal cancer: CT, endoscopic US, and FDG PET for assessment of response to neoadjuvant therapy - systematic review. Radiology 236: 841-851. Van Westreenen HL, Westerterp M, Jager PL, van Dullemen HM, Sloof GW, Comans EFI, van Lanschot JJ, Wiggers T, Plukker JT (2005) Synchronous primary neoplasms detected on 18 F-FDG PET in staging of patients with esophageal cancer. J Nucl Med 46: 1321-1325. Yaqub M, Boellaard R, Kropholler MA, Lammertsma AA (in press) Optimisation algorithms and weighting factors for analysis of dynamic PET data. Phys Med Biol. 12