Annual Report Nuclear Medicine & PET Research 2004-2005 1
Nuclear Medicine & PET Research
Annual Report 2004-2005
Annual Report Nuclear Medicine & PET Research 2004-2005 2
I. Introduction 3
II. Mission 4
III. Organisational structure 7
IV. Expertise and facilities 10
V. Patient care 13
VI. Education and professional training 17
VII. Research and development 19
VIII. Societal impact 25
IX. Current trends and perspectives 28
X. Personnel 30
XI. References 35
Annual Report Nuclear Medicine & PET Research 2004-2005 3
In 1997 the VU University Medical Centre (VUmc) initiated an interdepartmental PET project
(PET centre), following preparatory activities of the Department of Nuclear Medicine. The
mission of this PET centre was to combine methodological and clinical PET research with
diagnostic applications, the latter being focussed on the development of diagnostic guidelines.
Studies were performed in collaboration with the RadioNuclide Centre (RNC) of the VU
University (VU), active in radiochemistry research since 1975, and with the BV Cyclotron VU,
responsible for the production of the required radionuclides. Moreover, at the same time, the
RNC was equipped with an experimental PET scanner and GMP compliant radiochemistry
To guarantee a coherent approach with respect to the various PET activities, the board of
directors of VUmc and VU decided to combine all activities into a single department.
Consequently, on January 1st
, 2004, the VUmc Department of Nuclear Medicine & PET
Research was formed, incorporating the former Department of Nuclear Medicine, the PET
project and the RNC. Setting up the organisational structure of this new department took place
in 2004 and was finalised in 2005. The present report is the first annual report of the new
department, covering the years 2004 and 2005.
Annual Report Nuclear Medicine & PET Research 2004-2005 4
The integration of nuclear medicine facilities and expertise at the VU-campus allows for
operationalisation of this mission into a comprehensive spectrum of activities covering patient
care, education and training, and research.
The aim of the Department of Nuclear Medicine & PET Research to be an expert centre for the
development and application of PET, is in line with the ambition of the VUmc to be a
knowledge centre for health care.
PET was developed in the nineteenseventies as a non-invasive in vivo research technique for
pathophysiological investigations, which provided the possibility to obtain new information on
human disease. Over the last 10 to 15 years, it has been “discovered” as a sensitive diagnostic
technique, especially for detecting metastases in oncology, resulting in PET being the fastest
growing technique within the domain of medical technology todate. As a quantitative molecular
imaging technique, its potential for assessing effectiveness and action of therapy has also been
recognised. Several pharmaceutical companies have invested in their own PET facilities or
entered into a structural collaboration with a PET research centre in order to evaluate new drugs
in vivo. Given this potential, it will only be a matter of time before PET will be used for
The mission of the department is to develop, validate and implement radiopharmaceutical
(‘molecular’) technology for diagnosis and treatment of disease.
Annual Report Nuclear Medicine & PET Research 2004-2005 5
Based on the considerations given above, the Department of Nuclear Medicine & PET Research
has decided to focus its research on PET, as is highlighted in the name of the department. As
such, the activities of the department cover the entire process from biological hypotheses to
implementation of technologies into clinical practice, with the inherent ability to add to the
knowledge (both from conceptual and practical points of view) of diseases and their treatment.
The multidisciplinary expertise, brought together within the new department, and the
investments in infrastructure not only provide the means, but also create the moral obligation to
aim for a leading position in the world, in particular with respect to scientific PET research. The
department aims to achieve this goal within the next five years by continuously investing in
talented scientists, radiochemical research, modelling research and medical technology
ii. Patient care
The aim of the Department of Nuclear Medicine & PET Research is to provide state of the art
diagnostic and therapeutic nuclear medicine for the VUmc and as a referral centre for hospitals
without access to nuclear medicine facilities. Moreover, the present infrastructure finally allows
for newly developed technology to be clinically validated and implemented from within the
department, before dissemination into general practice, ie. to carry the technology from bench to
Annual Report Nuclear Medicine & PET Research 2004-2005 6
iii. Education and training
As an expert centre, it is the intention of the Department of Nuclear Medicine & PET Research
to take a leading role in the multidisciplinary education and training of professionals, working in
the field of nuclear medicine & PET research, as well as of those who are using this technology
for patient management. It is felt that this part of the mission directly follows from the
departments’s research activities and expertise in patient care. Standardisation and harmonisation
(from acquisition to interpretation) are the main challenges for new technologies in clinical
To achieve the aims mentioned above, the Department of Nuclear Medicine & PET Research
considers collaboration to be a key principle. The department continuously seeks collaboration
with research groups both within and outside the VUmc.
Annual Report Nuclear Medicine & PET Research 2004-2005 7
III. Organisational structure
On January 1st
, 2004, the newly formed Department of Nuclear Medicine & PET Research
comprised a staff of 76, originating from the former department of nuclear medicine, the RNC
and the PET project. The rationale behind this integration was to concentrate all expertise
related to the development and application of radionuclide tracers into one organisational unit in
order to guarantee a coherent an efficient approach to these activities.
Integration of the three parties mentioned above required an extensive reorganisation, especially
as it involved a change of employer (from VU to VUmc) for employees of the RNC. This
reorganisation was established following extensive consultation of all employees and according
to legal requirements for such a reorganisation. Many members of the new department made a
considerable effort into the process of reorganisation. Apart from the formal requirements, it
was recognised that a concerted approach was necessary to obtain a truly coherent department.
Following a general kick-off meeting in June 2004, several multidisciplinary working parties were
formed. These working groups formulated, discussed and, where necessary, proposed
alternatives for the previously determined essential processes within the department. Merging
preclinical and clinical fields and workers implied more than just a logistic manoeuvre. It also
required an adaptation to a different culture. Despite several complicating factors (prof. Teule
leaving for University Hospital Maastricht, followed by an open procedure for his succession;
unsuccessful procedure to find a suitable professor of radiofarmacochemistry and head of the
chemistry section), the formal process was completed in the fall of 2005.
The new Department of Nuclear Medicine & PET Research is divided in (professional) sections,
led by section heads. In addition, within each section, one or more coordinators have been
appointed, who are responsible for organising certain areas of work. Operational activities, such
as personnel, administration, finances and secretarial assistance, are embedded in a dedicated
operational office. Finally, there are two heads of department.
A diagram of the organisational structure of the Department of Nuclear Medicine & PET
Research is given below. This diagram also highlights that many activities are incorporated into
projects, both scientific and non-scientific.
Given the size of the new department and the very strong research component, it was decided to
appoint two heads of department, one responsible for patient care and professional training
(prof. G.J.J. Teule), the other for research and education (prof. A.A. Lammertsma). On
, 2004, prof. Teule took up a new position at the University Hospital of Maastricht
and dr. O.S. Hoekstra was appointed as acting head of department (patient care and professional
training). At the same time an open procedure was initiated to fill the vacant chair. As a result
of this procedure, dr. Hoekstra became full head of department for patient care and professional
training, and was appointed as full professor in Nuclear Medicine in November 2005.
As part of the reorganisation it was decided to create a new chair of radiopharmacochemistry, in
collaboration with the Faculty of Sciences and the BV Cyclotron VU. Holder of this chair would
become head of the chemistry section and, in line with the importance of radiochemistry for the
department, member of the managing team (MT), together with the heads of department and the
manager of Cluster I to which the department belongs. An international procedure to find a
suitable candidate was started in the second half of 2004. In the summer of 2005 it became clear
that no suitable candidate could be found. To guarantee continuity within the chemistry section,
prof. G.A.M.S. van Dongen was appointed as acting section head (and member MT). Although
his official appointment took effect on January 1st
, 2006, he already was involved in a consulting
role during the last months of 2005.
Annual Report Nuclear Medicine & PET Research 2004-2005 8
Finally, prof. J.E. Leysen joined the department in a consulting role from November 1st
Formerly, she fulfilled this role at the Department of Pharmacology. As this department was
reorganised and prof. Leysen had a strong interest in molecular imaging, a move to the
Department of Nuclear Medicine & PET Research was logical, thereby substantially
strengthening pharmacological knowledge within the department.
Annual Report Nuclear Medicine & PET Research 2004-2005 9
Organisational Structure Department of Nuclear Medicine & PET Research
Office / lab space
Head of Department
Head of Department
Abbreviations used - GMP: good medical practice; NIAZ: Nederlands Instituut voor Accreditatie van Ziekenhuizen; RNL: radionuclide laboratory
Annual Report Nuclear Medicine & PET Research 2004-2005 10
IV. Expertise and facilities
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
i. Available tracers
Licensed PET radiopharmaceuticals
C labelled: flumazenil, PK11195, raclopride, verapamil, R116301, palmitate, R107474,
F labelled: FDG, FLT, fluoride, FP-β-CIT, MPPF, FDDNP, proline.
O labelled: H2O, O2,, CO, CO2.
C labelled: docetaxel, WAY100635, deprenyl, methionine.
N labelled: N2.
F labelled: FAZA, fluoromethylcholine.
Licensed SPECT radiopharmaceuticals
I labelled: R91150, iomazenil, hippuran, iodine, MIBG, β-CIT.
Monoclonal antibodies and peptides
Validated and universal procedures are in place for labeling antibodies and peptides for
pharmacokinetics/biodistribution studies (99m
Lu), SPECT imaging
Lu), PET imaging (68
I) and radioimmunotherapy (186
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.
ii. Available analytical methods
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
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,
Annual Report Nuclear Medicine & PET Research 2004-2005 11
central (GABAA) and peripheral benzodiazepine receptors, serotonin 5-HT1A receptors, NK1
iii. Available biological methods
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).
Rats, mice, rabbits, minipigs, rhesus monkeys, transgenic mice, nude mice and rats.
Oncology: breast, cervical, head & neck, lung, prostate and colon cancer, glioma.
Neurology: Parkinson’s disease, depression, neurotrauma, MS, epilepsy.
iv. Clinical research studies
Medical technology assessment (MTA), PET in drug development.
Alzheimer’s and Parkinson’s disease, epilepsy.
Anxiety & depression, schizophrenia, post traumatic stress disorder.
Myocardial ischemia, heart failure.
Oncology (only main studies)
Lung, breast and head & neck cancer, response monitoring (chemo- & radiotherapy).
State-of-the-art whole body PET camera (HR+, CTI/Siemens);
High resolution research PET camera (HRRT, CTI/Siemens);
3 gamma cameras (2 dual-head systems, Siemens);
3 therapy rooms (located within the ward of the department of haematology);
Several gamma probes (including a laparoscopic probe);
Medrad infusion system (controlled injections/infusions);
Veenstra on-line blood withdrawal & detection systems;
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;
Annual Report Nuclear Medicine & PET Research 2004-2005 12
Small animal housing facilities;
Multiple HPLC and GC systems;
Multiple gammacounters and betacounters;
In addition, radioactivity is produced by BV Cyclotron VU (general manager Dr. P.J. van der
Jagt), where the following facilities are available:
Philips AVF 30 cyclotron;
2 IBA 18/9 cyclotrons;
Commercial production of [18
F]FDG, and 81m
Kr and 123
I labelled products.
Annual Report Nuclear Medicine & PET Research 2004-2005 13
V. Patient care
It will be clear that, with respect to patient care, there are relationships with most departments of
VUmc. Traditionally, there have been strong collaborations with the departments of internal
medicine (in particular endocrinology, pulmonology, haematology and medical oncology),
cardiology, surgery, otolaryngology, neurology, orthopedics, pediatrics, and more recently with
the department of clinical epidemiology & biostatistics as a result of the PET technology
assessment efforts. Since the introduction of PET in 1997, the required co-reading with
radiological tomographic imaging (CT, MRI) has induced a tight interaction between dedicated
radiologists of the VUmc and nuclear medicine physicians. The existing collaboration with the
department of radiology will intensify after the installation of the planned PET-CT scanner in
2006. The same will be true for the collaboration with radiotherapy, as this scanner will partly be
used for treatment planning.
In oncology, the geographic target area is the the region administered by the Comprehensive
Cancer Centre Amsterdam (IKA). In neurology, the department plays a national role for
diagnostics in the presurgical work-up of patients with medically refractary epilepsy.
After transferring the at the time substantial number of bone density measurements (DEXA) to
the department of radiology (2001), the range of activities has been dynamic, primarily due to
developments related to PET. The total number of activities, however, is rather stable at 8000
per year, with an obvious trend towards more complex procedures, especially in the PET
domain. The main activities are listed in the table below.
cardiology 2212 (7%*) 2345 (9%)
endocrinology 818 (4%) 722 (4%)
inflammation 74 (70%) 94 (88%)
nephrology 334 (0%) 358 (0%)
neurology 185 (74%) 217 (63%)
oncology 1355 (60%) 1447 (60%)
pulmonology 1619 (37%) 1392 (52%)
skeletal 963 (0%) 1074 (0%)
miscellaneous diagnostic 39 (0%) 71 (0%)
therapy 243 210
* percentage PET procedures
The relative contribution of PET procedures to the total number of nuclear medicine
investigations has increased steadily over time, in line with international trends. Without new
facilities, no further increase would be possible, since the scanner capacity is fully exploited. The
vast majority of PET scans was for oncological purposes, with 50% being performed for
hospitals other than the VUmc. The main indications were lung cancer, malignant lymphoma
and colorectal cancer.
To promote effective use of the nationwide limited capacity, a policy was adopted in which
clinicians were obliged to consult attending nuclear medicine physicians before referring patients
for PET. The only exceptions were scans for indications that already had been incorporated into
guidelines. For these ‘guideline-scans’ dedicated slots were reserved to limit waiting lists. From
Annual Report Nuclear Medicine & PET Research 2004-2005 14
time to time, the scanner had to be restricted for referring physicians within the IKA region to
avoid unacceptable waiting lists for patients in the VUmc’s geographical area. In 2005, however,
it was necessary to work in shifts in order to cope with the increasing number of valid requests.
Finally, to optimise the use of PET in general, the department actively contributed to all national
multicentre studies evaluating the cost-effectiveness of FDG PET in oncology.
Several years ago, the department chose to focus on PET and to deliberately refrain from several
nuclear medicine activities, such as 131
I-MIBG therapy and 123
I DAT SPECT. In order to
concentrate expertise, those patients were referred to neighbouring centres.
The department actively contributed to multicentre studies (ANTELOPE projects) investigating
the role of CT angiography for diagnosis of pulmonary embolism. This development has
contributed to the relative increase of PET within the pulmonology domain. In addition,
inflammatory processes were increasingly diagnosed and monitored using FDG PET rather than
In and 67
Ga labelled compounds. In cardiology, SPECT studies (diagnosis of ischaemia
and assessment of viability) comprised 90% of the non-PET procedures. Finally, dissemination
I therapy facilities tended to increase the relative proportion of high dose therapies for
patients with thyroid cancer. In 2006, a national guideline on thyroid cancer is expected, which
should address the appropriate balance between diffusion of this technology and the need to
maintain expertise within a multidisciplinary setting.
i. Incidents related to patient care
In 2004 and 2005, six incidents were reported, three in each year. Five were related to lack of
compliance with internal rules and regulations, four of which occurred in the setting of routine
patient care and one in the research area.
Incorrect radiopharmacon prepared for cardiology stress test study; discovered prior to
injection; examination rescheduled.
Background: deliberate deviation from routine procedure ordered by nuclear medicine
physician (Tl-201 rather than Tc-99m-Myoview) not recognized by administrative section.
Action: signaling system for specific protocol deviations.
Examination filed incorrectly by technologist (wrong patient name); discovered by head of
technology section and corrected prior to archiving.
Background: human error in combination with lack of automated check procedure.
Action: manufacturer software contacted, but no solution provided; in-house developed
software procedure installed.
During five subsequent stress tests, administered adenosine dosage too low; patients
Background: series of errors: department of pharmacy incorrectly delivered 40 microgram/l
dosages rather than 6 mg/ml; technologist and attending physician failed to check dosage.
Action: pharmacy checks dosages prior to delivery; double check by technologist / physician
prior to any injection; drug label adhered to medical record.
Incorrect radiopharmaceutical administered (18
FDG rather than 11
Background: protocol violation (see above), partly induced by time pressure at PET.
Action: repeated instruction (see January 2005).
Annual Report Nuclear Medicine & PET Research 2004-2005 15
Patient complaining of partial hypesthesia at first digit after arterial cannulation for research
Background: retrospective complaint; no irregularities during PET examination.
Action: referral to vascular surgeon: no objective abnormalities; expectative policy.
The remaining incident was a complaint concerning extensive delay of transportation back to the
referring hospital due to failing ambulance logistics.
ii. Radiation safety
Administration of radiation safety, as required by Dutch law (Kernenergiewet), can be found in
the annual reports by the “dienst Veiligheid & Milieu”. These reports can be found at the VU
intranet site https://www.intranet.vu.nl/Arbo_en_Milieu/index.cfm.
iii. Patient satisfaction survey
The department presented and internally discussed the results of an internally designed and
managed survey on patient satisfaction early 2004. The survey pertained to the 2nd
half of 2003
and was in fact a follow-up to a similar procedure in 1998. Within a time frame of two months,
a questionnaire with 20 multiple-choice questions was mailed to 286 patients, a few days after
they had undergone a diagnostic or therapeutic procedure in the department. The survey
comprised a mix of in-patients and out-patients, who had been referred for conventional nuclear
medicine procedures or PET, both from within the VUmc and from other hospitals, and who
represented a range of age categories. At the time of the patient’s visit, employees of the
department were unaware whether the patient would be approached, but they were aware that
the survey was running. The complete (Dutch) version is available from the secretariat of the
The survey pertained to items on waiting lists (actual and subjective perception), flexibility of the
department to adapt scheduling of the procedures to the patient’s preferences, quality and actual
delivery of pre-test information (verbal, leaflets), logistic procedures at the time of scanning
(delays, communication), attitude of personnel, quality (spatial, privacy) and hygienic state of
waiting and scanning rooms, and finally a subjective assessment of the full procedure.
The response rate was 57% (compared to 50% in 1998). The findings are summarized in the
a. Average results of answers to the summarising question ‘how would you rate this department on….’ on a scale
of 1-10 (1: extremely poor … 10: excellent); NM = nuclear medicine.
NM 1998 NM 2003 PET 1998 PET 2003
Pre-test information 8.1 7.6 7.8 8.1
Attitude of staff 8.5 8.4 8.4 8.6
Attention for privacy 8.4 8.2 8.1 8.4
Facilities 7.7 7.6 7.4 7.9
General impression 8.1 8.0 8.2 8.2
Annual Report Nuclear Medicine & PET Research 2004-2005 16
b. Relative proportion (%) of ratings below ‘7’
NM 1998 NM 2003 PET 1998 PET 2003
Pre-test information 10.5 16.8 15.8 7.7
Attitude of staff 3.8 4.0 5.3 1.9
Attention for privacy 4.1 5.4 0.0 4.1
Facilities 18.4 17.2 26.3 11.5
General impression 5.9 3.3 10.0 6.1
Even though it was felt that results in 1998 had been encouraging, a few issues needed
improvement: there were apparent deficiencies in the patient information process, especially for
PET (at the time, PET had been operational for just one year). More specifically, available
patient information leaflets were not adequately distributed when scans were ordered.
Interestingly, patients reported that employees of the department compensated for this lack of
written material by providing adequate information at the time of the procedure. Nevertheless,
efforts were undertaken to improve the quality and availability of written material. Moreover, for
PET, the survey had not distinguished between patients referred for diagnostic and research
procedures. Therefore a more detailed survey on the quality of information for PET procedures
was performed (conducted by A. Giacomo-Russo, supervised by prof E. van Leeuwen). Based
on the outcome of this survey, procedures were adapted, apparently with success. Finally,
criticism was most prominent with respect to the lack of adequate facilities within the
department. This is a longstanding problem (not uncommon in VUmc), which indeed urgently
Annual Report Nuclear Medicine & PET Research 2004-2005 17
VI. Education and professional training
i. Undergraduate and graduate education
In 2005, the VUmc rigorously changed the format of its basic medical training curriculum (see
http://www.vumc.nl/hoofdframes/onderwijs/index.html). Since then, the Department of
Nuclear Medicine & PET research provides tutors for training of first-year students (in
2005/2006: drs A.A. Geldof and E.F.I. Comans). In the ‘old’ curriculum, the department
provided several lectures in the initial three years of medical training, took part in or organised
several practical courses, organised on-site courses for medical interns and provided supervised
training for individual students. Several members of staff contributed to courses organised by
the VUmc research institutes, to their master student programs and/or supervised training for
individual students. Via the Department of Clinical Epidemiology and Biostatistics, Hoekstra
provided several practical courses to undergraduate students regarding critical appraisal of
literature on diagnostic tests.
Apart from involvement in education of medical students, members of staff also contributed by
giving lectures at undergraduate courses of the Faculty of Sciences (Medical Natural Sciences
track) and the Faculty of Psychology and Education (Neuropsychology track) of the VU. In
addition lectures were given for the Technical University of Delft (Medical Physics programme).
In addition to lectures the department received students for extended periods of time (3 to 9
months) of supervised scientific training from the Faculty of Sciences (Medical Natural Sciences
track) and the Faculty of Earth and Life Sciences (Medical Natural Sciences track) of the VU.
Finally, lectures were given at several local and national graduate courses.
ii. Postgraduate education in PET
With the advent of PET in clinical practice, standardisation again is a major topic in nuclear
medicine. Furthermore, to keep pace with the rapid diffusion of PET in Dutch clinical practice,
skills need to be disseminated and implemented. This applies to pre- and postgraduate settings
with regard to both diagnostic (nuclear medicine physicians, radiologists) and referring
specialists. Based on the remit of academic medicine, the department has taken the lead in
developing educational activities in relation to PET, at the level of both medicine and physics.
In 2000, when carrying out the top-down national research health care programme on PET, a
lack of appropriate postgraduate learning facilities for PET were recognized. In addition,
experience at the EANM (European Association of Nuclear Medicine) teaching facility in Vienna
(Comans) suggested that a more intensive and active programme was required. In an attempt to
further professionalise this training, Comans became a member of the NVMO (Dutch Society
for Medical Education) and took courses in didactics.
Since then, the Department of Nuclear Medicine & PET Research has organised several cycles
of courses on oncological PET in a skills lab format. For this purpose, an extensive structured
PET database was set up, and there was active and enthousiastic expertise input from the VUmc
departments of pulmonology (dr. E.F. Smit), surgery (dr. M.A. Paul), otolaryngology (dr. R. de
Bree), haematology (dr. J. Zijlstra-Baalbergen) and clinical epidemiology & biostatistics (prof. dr.
M. Boers). Teaching files were prepared with the help of several medical and PhD students.
Course participants came from community hospitals in the Netherlands, both within and beyond
the catchment area of the Comprehensive Cancer Centre Amsterdam (IKA). Especially the link
with the Comprehensive Cancer Centre South (IKZ, Eindhoven) became tight, resulting in IKZ
inviting one of the NGP staff members (Hoekstra) to become one of their two PET consultants.
Annual Report Nuclear Medicine & PET Research 2004-2005 18
Finally, since 2004, NGP provides the in-house PET training of the nuclear medicine residents
of the University Medical Centre Leiden, which at present does not have its own PET facility.
Recognizing that education of referring clinicians might be an important tool to promote
effective use of PET, the department became involved in pre- and postgraduate courses for
surgeons, radiologists, pulmonologists and medical oncologists. In addition, members of the
department often (about 20 times) were invited by medical staff of community or university
hospitals, by their board of directors, or by tumour working groups of comprehensive cancer
centres to give lectures and/or discuss the details of PET in clinical practice. Moreover, it was
recognized that educating the principles of nuclear medicine to those working in preclinical
science was equally important to stimulate the field. Therefore, lectures were also given at the
annual courses of the NVVO (Dutch Society of Oncology). Finally, Lammertsma was involved
in the organisation of the (on average biannual) international PET Pharmacokinetic Course, in
which the first principles of tracer kinetic modelling, a prerequisite for quantitative PET studies,
iii. Professional training
As member of the board of the Dutch Society of Nuclear Medicine (NVNG), Comans had taken
the initiative to modernise the training of nuclear medicine residents in 2001. From 2004, he
actively participated in the working party on restructuring nuclear medicine training of residents
(WEMONG). Pijpers chaired the NVNG’s educational committee, which organised the annual
courses for nuclear medicine residents, and all members of staff (physicians as well as physicists)
actively contributed to these courses. Finally, Lammertsma was chairman of the Executive
Committee for Board Registration of the Dutch Society of Clinical Physics and, as such,
responsible for the quality of training of clinical physicists in the Netherlands.
Over 2004 and 2005, the Department of Nuclear Medicine & PET Research was responsible for,
on average, the training of five residents in nuclear medicine (responsible physicians: prof. G.J.J.
Teule/dr. J.C. Roos until Sept 1st
, 2004; dr. R. Pijpers/dr. O.S. Hoekstra thereafter). A total of
five completed their training within this period, and several of them took additional PET courses
during fellowships at the department. In addition, the department was responsible for, on
average, the training of four residents in clinical physics (responsible physicist: dr. A. van
Lingen), with one completing his training within this period. Moreover, ten nuclear medicine
technologists followed their in-service training in the department (responsible technologist:
C.S.M. de Jong-Greuter), with all but one finishing their training within the reporting period.
Finally, three pharmacists performed a research project within the department as part of their
iv. Education in radiation safety
Both in 2004 and 2005 the department organised (coordinator: dr. G.W.M. Visser) 5 courses
“Working with radioactivity”. This course is compulsory for VU and VUmc personnel, who
need to handle radioactivity as part of their job. The course is at such a level that participants are
sufficiently equipped to take the (state) examination radiation safety level 5B. In addition,
members of the department lecture at incidental radiation safety courses organised by the
radiation safety group of the VU. Finally, members of the department provide radiation safety
seminars and instructions for trainees and students, whose stay at the department is too short to
be able to follow the more formal course mentioned above.
Annual Report Nuclear Medicine & PET Research 2004-2005 19
Nearly all research of the Department of Nuclear Medicine & PET Research is embedded within
four VUmc based research institutes (V-ICI, ICEN, IcaR-VU, MOVE) and one VU/UL
research institute (LACDR), the latter primarily covering radiochemistry research.
V-ICI: VUmc Institute for Cancer and Immunology
ICEN: Institute for Clinical and Experimental Neuroscience
ICaR-VU: Institute for Cardiovascular Research
MOVE: Institute for human movement research
LACDR: Leiden/Amsterdam Centre for Drug Research
The only exceptions are a number of research projects, which are carried out in collaboration
with groups outside the VUmc. Most scientific research is carried out in collaboration with
other groups, both from within and outside VUmc. This is best illustrated by the large number
of PhD students from various departments, who perform their research within the Department
of Nuclear Medicine & PET Research.
The (former) department of nuclear medicine had a tradition of research related to the sentinel
node procedure and, in collaboration with the department of cardiology, myocardial viability.
After the introduction of PET at the VUmc in 1997, research progressively shifted towards PET.
Initially, focus was on MTA studies of clinical applications of FDG PET in oncology. In
addition, research concentrated on the development of quantitative procedures for routine
clinical use. These procedures are now used in prospective patient studies.
The steady increase of neuroreceptor ligands, together with the presence of an experimental high
resolution scanner (HRRT), have led to a more prominent role of the neurosciences. This is in
line with the wish of both VUmc and VU to excel in brain imaging. In addition, existing
expertise in the areas of radiochemistry and modelling (development of new tracers and tracer
kinetic procedures) has resulted in a research line investigating the use of PET in drug
After the formal integration of the three entities (nuclear medicine, PET project, RNC), a formal
project administration system was set up to better coordinate and streamline the various research
i. PhD students
During 2004 and 2005 a total of nearly 50 PhD students performed research at the Department
of Nuclear Medicine & PET Research, with the vast majority performing research in PET. More
than half of these students performed their entire PhD research within the department. For the
remainder PET constituted part of their PhD studies. Four PhD candidates defended their
thesis successfully in 2004 or 2005. Most of the (applied) PhD projects were performed in
collaboration with other departments. A complete list of PhD students is given under
Personnel, where also involvement of other departments or institutes is indicated.
Annual Report Nuclear Medicine & PET Research 2004-2005 20
Ongoing january 1st
1. FDG PET top-down program ZON-MW:
a.Positron emission tomography for the prediction of long-term treatment outcome in newly
diagnosed aggressive Non-Hodgkin’s lymphoma (PALET); prospective multicentre
observational study; funded by ZON-MW grant no. 945-11-003 (VUmc investigators: J
Zijlstra, EFI Comans, OS Hoekstra, depts of nuclear medicine & PET research and
b.PET and colorectal liver metastases (POLEM); multicentre randomized trial; funded by
ZON-MW grant no. 945-11-017 (VUmc investigators: EFI Comans, J van der Sijp; depts
of nuclear medicine & PET research and surgical oncology).
c.Improving and simplifying diagnostic evaluation of esophageal cancer with a combination
EUS-FNA and PET (DIVAPEC); prospective multicentre observational study; funded by
ZON-MW grant no. 945-11-002 (VUmc investigators: EFI Comans, OS Hoekstra, dept of
nuclear medicine & PET research).
d.Screening for distant metastases and second primary tumours with FDG-PET (SCHOOL).
prospective multicentre observational study; funded by ZON-MW grant no. 945-11-014
(VUmc investigators: A Senft, R de Bree, OS Hoekstra; depts of nuclear medicine & PET
research and otolaryngology).
e.PRIMUS (unknown PRIMary tumours Studied with FDG-PET); prospective multicentre
observational study; funded by ZON-MW grant no. 945-11-005 (VUmc investigators: R de
Bree, OS Hoekstra, depts of nuclear medicine & PET research and otolaryngology).
2. The role of excitatory amino acids in neuronal damage and outcome after traumatic brain
injury: assessment in patients using microdialysis and (r)-11C PK11195 PET; grant from
Hersenstichting Nederland; single centre study (H Folkersma, BNM van Berckel, W
Vandertop, AA Lammertsma; depts of nuclear medicine & PET research and neurosurgery).
3. Development of the long-lived positron emitters 89
Zr en 124
I; grant from NWO/Stichting
Technische Wetenschappen (L Perk, GAMS van Dongen, JDM Herscheid, GWM Visser;
depts of nuclear medicine & PET research and otolaryngology).
4. Selective targeting of angiogenesis and of tumor stroma (STROMA); grant from EU, 6th
framework (B Tijink, GAMS van Dongen; depts of nuclear medicine & PET research and
5. Experimental and clinical studies using positron emission tomography (PET) for monitoring
response to chemotherapy in (locally) advanced breast cancer; grant from KWF no VU2003-
2822 (WGE Direcks, CFM Molthoff, G Giaccone, AA Lammertsma; depts of nuclear
medicine & PET research and medical oncology).
6. Development of PET methodology for monitoring early responses to chemotherapy in
breast cancer patients; grant from The Susan G. Komen Breast Cancer Foundation US
Grant #IMG0402756 (J Emmering, JJM van der Hoeven, CFM Molthoff, M Lubberink, AA
Lammertsma, OS Hoekstra; depts nuclear medicine & PET research and internal medicine
7. PIRAMID (Pathophysiological significance of myocardial triglyceride accumulation in type 2
diabetes mellitus related heart disease: the effect of pioglitazone on myocardial metabolism
and function); grant from Eli Lilly NL, single centre study (VUmc investigators: L Rijzewijk,
M Diamant, AA Lammertsma, HWAM de Jong; depts of nuclear medicine & PET research,
cardiology and endocrinology).
8. Mechanisms of pharmacoresistance: longitudinal Positron Emission Tomography studies in
experimental models of epilepsy; grant from the NEF no 02-06 (VUmc investigator: AA
Lammertsma; dept nuclear medicine & PET research; in collaboration with department of
Annual Report Nuclear Medicine & PET Research 2004-2005 21
9. Concerted Action: Neuroreceptor changes in mild cognitive impairment; European
Commission, Contract QLK6-CT-2000-00502 (VUmc investigators: A Schuitemaker, M
Kropholler, M Lubberink, R Boellaard, B van Berckel, P Scheltens, AA Lammertsma; depts
of nuclear medicine & PET research and neurology).
10. Potential of positron emission tomography with Zirconium-89-labeled chimeric monoclonal
antibody U36 for planning of radioimmunotherapy in head and neck cancer patients; grant
from KWF no 2000-2155 (GAMS van Dongen, R de Bree, AA Lammertsma; depts of
nuclear medicine & PET research and otolaryngology).
Acquired in 2004-2005
1. PET of cerebral amyloid load as a potential diagnostic marker for pre-symptomatic
Alzheimer’s disease; grant from American Health Assistance Association, single centre study
(N Tolboom, BNM van Berckel, Ph Scheltens; depts of nuclear medicine & PET research
2. Imaging of amyloid in pre-symptomatic Alzheimer’s disease; grant from Internationale
Stichting Alzheimer Onderzoek, single centre study (N Tolboom, BNM van Berckel, Ph
Scheltens; depts of nuclear medicine & PET research and neurology).
3. From hypothesis towards data-driven analysis of neuroreceptor studies with positron
emisison tomography; grant from NWO: VIDI 016.066.309 (J Mourik, F van Velden, R
Boellaard; dept of nuclear medicine & PET research).
4. Bridgehead labelling; grant from NWO STW (VUmc investigator: JDM Herscheid; dept of
nuclear medicine & PET research).
5. Accuracy of 18
FDG-PET and spiral CT for the early prediction of non-response to
preoperative chemoradiotherapy in patients with esophageal cancer (NEOPEC); multicentre
prospective observational study; grant from ZON-MW 945-04-510 (VUmc investigators: R
Boellaard, EF Comans, M Cuesta, OS Hoekstra; depts of nuclear medicine & PET research
and surgical oncology).
FDG-PET for avoidance of futile direct laryngoscopies under general anaesthesia with
taking of biopsies in patients with suspicion on recurrent laryngeal carcinoma after
radiotherapy (RELAPS); multicentre prospective observational study; grant from ZON-MW
no. 945-04-311 (VUmc investigators: L van der Putten, R de Bree, EFI Comans, C Uyl-de
Groot, M Boers, CR Leemans; depts of nuclear medicine & PET research, otolarynogology
and clinical epidemiology & biostatistics).
7. Nanobodies tegen tumoren en neurodegeneratieve ziekten; grant from Ablynx (GAMS van
Dongen; depts of otolaryngology and nuclear medicine & PET research).
8. Synthesis and evaluation in tumor bearing mice of [18
F]ML10 as a potential PET imaging
ligand for apoptosis; collaboration with NST Neurosurvival Technologies, Israel (AD
Windhorst, GAMS van Dongen; dept of nuclear medicine & PET research).
C docetaxel in oncology; grant from Treucom/SBGO (NH Hendrikse, OS Hoekstra, AA
Lammertsma; dept of nuclear medicine & PET research).
FDG PET response evaluation of chemoradiation in pancreatic cancer (PANTAR); grant
from Roche, single centre observational study (B van Triest, B Kunnen, OS Hoekstra; depts
of radiation therapy, medical oncology and nuclear medicine & PET research).
11. FDG and H2
O PET response evaluation in lung cancer (bT); grant from Roche,
multicentre observational study (EF Smit, OS Hoekstra; depts of pulmonology and nuclear
medicine & PET research).
12. Preventie en vroegdiagnostiek van prostaatkanker: de toepassing van groeisignaal-evaluatie
voor de voorspelling van tumor gedrag; grant from CCA (postcode-loterij); (RJA van
Moorselaar, AA Geldof; depts of nuclear medicine & PET research and urology).
13. Evaluation of [C-11]R116301 as a tracer for in vivo quantification of NK1 receptors in human
subjects; Clinical Study Agreement with Johnson&Johnson Pharmaceuticals, L.L.C. North
Annual Report Nuclear Medicine & PET Research 2004-2005 22
Brunswick (SPA Wolfensberger, AJ Airaksinen, BNM van Berckel, R Boellaard, DJ Veltman,
AD Windhorst, JE Leysen, AA Lammertsma).
During the period 2004-2005 members of the Department of Nuclear Medicine & PET research
authored or co-authored some 100 papers, which appeared in international peer reviewed
journals. In addition, four PhD theses were published. A complete list of published national
and international papers is given under References.
Herscheid JDM, Verbeek J – Bridgehead labelled radiopharmaceuticals – EP patent 05075259.1,
1. P Verboom et al. EANM Springer award best clinical paper (2004)
2. NM Bruin et al. EANM Springer award best scientific paper Technology (2004)
3. CM van Rij. Winner Woldring Prijs 2004 (NVNG) for best scientific presentation.
vi. Invited talks (international)
1. Boellaard R. Influence of the decay spectrum on the quantification of “Dirty Isotopes”;
First symposium “124-I in biological and medical application”, September 30 – October 1,
2005, Essen, Germany.
2. Geldof AA. Gossypol enhances radiation effects in human prostate cancer cells; 9th
Wolfsberg Meeting, June 18-20, 2005, Ermatingen, Switserland.
3. Hoekstra OS. Towards valid markers of response: the EORTC experience; NCI Workshop
on The Role of FDG PET in the Evaluation of Therapeutic Response in Cancer, January 10-
11, 2005, Washington DC, USA.
4. Hoekstra OS. EORTC laboratory research groups: activities, aims and objectives of
the functional imaging group; 25th
Winter meeting of the EORTC – Pharmacology and
Molecular Mechanisms Group, January 28-31, 2004, Bradford, UK.
5. Hoekstra OS. Towards valid markers of response: the case of PET; Annual Meeting of the
European Society of Radiotherapy, October 24-28, 2004, Amsterdam, Netherlands.
6. Hoekstra OS. Should a PET scan be a requirement for optimal cancer management? Annual
Meeting of the European Society of Medical Oncology, October 29 – November 2, 2004,
7. Hendrikse NH. Visualization of physiological functions – imaging of P-glycoprotein
transport with positron emission tomography (PET); First International Symposium on
Resistant Cells “To die or not to die, is that resistant?”, May 6, 2005, Gwanju, South Korea.
8. Lammertsma AA.. Role of human and animal PET studies in drug development;
International Workshop on Quantitation in Biomedicel Imaging with PET and MRI, January
26-27, 2004, Osaka, Japan.
Annual Report Nuclear Medicine & PET Research 2004-2005 23
9. Lammertsma AA. Technological developments of fusion imaging; PET and Fusion (CT)
Imaging in Cardiology: Diagnostic and Clinical Perspectives; February 19-20, 2004, London,
10. Lammertsma AA. Qualitative and quantitative analyses; NCI Workshop on the Role of
FDG PET in the Evaluation of Therapeutic Response in Cancer, January 10-11, 2005,
Washington DC, USA.
11. Lammertsma AA. Dedicated brain scanners – opportunities and pitfalls; X Turku PET
Symposium, May 28-31, 2005, Turku, Finland.
12. Lammertsma AA. Dedicated brain scanners: opportunities and pitfalls; Towards a next
generation of high-resolution PET scanners, September 29-30, 2005, Delft, The Netherlands.
13. Lammertsma AA. Methods for definition of regions of interest and statistical models for the
brain; Annual Congress of the European Association of Nuclear Medicine, October 15-19,
2005, Istanbul, Turkey.
14. Lammertsma AA. How should we analyse FDG-PET studies for monitoring tumor
response? Workshop Biological Imaging for Therapy Selection and Tumor Response
Monitoring, December 3, 2005, München, Germany.
15. Lubberink M. Quantitative positron emission tomography for drug development and
imaging treatment response – requirements and pitfalls; 26th
Winter meeting of the EORTC
– Pharmacology and Molecular Mechanisms Group, January 26-29, 2005, Arcachon, France.
16. Molthoff CFM. Ovarian cancer and MOv18: the Amsterdam experience; what did we learn?
Clinical Advisory Meeting Morphotec Inc., March 22-24, 2004, Philadelphia, USA.
17. Molthoff CFM. Early assessment of response to chemotherapy in breast cancer using
positron emission tomography; The Susan G. Komen Breast Cancer Foundation’s eighth
Annual Mission Conference, A Promise in Action, June 5-7, 2005, Washington DC, USA.
18. Molthoff CFM. Biological correlates of [18
F]FDG uptake in cancer; Fourth Annual Meeting
of the Society of Molecular Imaging; September 7-10, 2005, Cologne, Germany.
19. Pijpers R. Sentinel node in head and neck cancer; Annual Congress of the European
Association of Nuclear Medicine, October 15-19, 2005, Istanbul, Turkey.
20. Schuitemaker A. Imaging of inflammatory processes in MCI-patients. Annual Congress of
the European Association of Nuclear Medicine, October 15-19, 2005, Istanbul, Turkey.
vii. International collaborations
Listed are those international collaborations that have resulted in a joint publication in 2004 or
2005, or that involved a visit of at least one month during the same period.
1. Van Berckel BNM – Laruelle M, Columbia University, New York, USA.
2. De Jong HWAM, Boellaard R – Wienhard K and co-workers, Max Planck Institute for
Neurologische Forschung, Cologne, Germany.
3. De Jong HWAM – Lenox M and co-workers, CPS Molecular Imaging, Knoxville, TN, USA.
4. De Jong HWAM, Lammertsma AA – Collaboration within a network of 14 PET groups in
Europe and North America to perform a multi centre HRRT performance investigation.
5. Lammertsma AA – Hatazawa J, Maruyama K, Osaka University, Osaka, Japan.
6. Lammertsma AA, van Berckel BNM, Boellaard R, Lubberink M, Kropholler M,
Schuitemaker A – EC concerted action “Neuroreceptor changes in mild cognitive
impairment”, together with groups from Copenhagen, Stockholm, Uppsala and Naples.
7. Lammertsma AA, Boellaard R – Cammici PG, Rimoldi O, Medical Research Council Clinical
Sciences Centre, London, UK
8. Lammertsma AA, Boellaard R – Schäfers KP, University of Münster, Münster, Germany.
Annual Report Nuclear Medicine & PET Research 2004-2005 24
9. Lammertsma AA, Boellaard R, Lubberink M – Jones T, Price P, Rajasekharan S, Manchester
Molecular Imaging Centre, Manchester, UK.
10. Lubberink M – Lundqvist H, Sandström M, Uppsala University and Uppsala University
Hospital, Uppsala, Sweden.
11. Lubberink M – Bergström M, Razifar P, Uppsala University and Uppsala Imanet AB,
12. Molthoff CFM – Herlyn D, Wistar Institute, Philadelphia, USA.
13. Molthoff CFM – Enger PO, Neuro Oncology, University of Bergen, Bergen, Norway.
14. Windhorst AD – Eisenhut M, DKFZ Heidelberg, Germany.
Annual Report Nuclear Medicine & PET Research 2004-2005 25
VIII. Societal impact
Many members of the Department of Nuclear Medicine & PET Research are active in
supporting scientific progress with respect to nuclear medicine and in implementing novel
nuclear medicine technology into routine patient care.
i. Development of guilines
The final step following evaluation of a diagnostic technology is the development of guidelines
for its proper use. Keeping in line with the mission of the department, several of its members of
staff were actively engaged in this activity, usually following a mandate from their professional
society. In recent years, the development of guidelines has switched from consensus to evidence
based procedures. This is an important step forward, but it also is more demanding for the
professionals involved in drafting these guidelines. In the period 2004-2005, three national CBO
(Dutch Institute for Healthcare Improvement) guidelines with active contributions from
members of the department were published:
1. Richtlijn Niet-Kleincellig longcarcinoom: stadiëring en behandeling. 2004, uitg. van
Zuiden, Alphen a/d Rijn (VUmc: OS Hoekstra).
2. Richtlijn Non-Hodgkin Lymfoom. 2004, uitg. van Zuiden, Alphen a/d Rijn. (VUmc: OS
3. Behandeling van het mammacarcinoom. 2005, uitg. van Zuiden, Alphen a/d Rijn
(VUmc: R Pijpers).
Moreover, members of the department directly participated in the development of guidelines on
diagnosis and management of hepatic metastases (VUmc: EFI Comans), and indirectly to the
one on esophageal cancer (for which GWM Sloof, AMC, was the NVNG delegate).
The knowledge on quantitative PET methodology was actively disseminated (other than by
publications) by Boellaard, as member of the NVNG/NVKF joint committee “Acceptatietesten
en kwaliteitscontrole van PET camera’s”.
ii. Member expert committees
The Dutch Cancer Foundation KWF installed a multidisciplinary committee to explore future
scenarios with respect to cancer imaging. The final report (Signaleringscommissie KWF.
Beeldvormende technieken binnen de kankerbestrijding: Vizier op de toekomst; Van den
Boogaard, Oisterwijk, 2005; VUmc: OS Hoekstra) included an outlook which accounted for
epidemiological as well as technological trends.
To finalize the topdown round and to wrap up the current position of PET in the Netherlands,
ZON-MW installed a working party, of which OS Hoekstra is a member.
The Netherlands Heart Foundation installed an expert committee to investigate the (potential)
role of imaging techniques in cardiovascular diseases and the need for further research. The final
report (Image guided strategies in cardiovascular disease; VUmc participant: AA Lammertsma)
will appear in 2006.
iii. Organisation of courses, meetings and workshops
1. Lammertsma AA, van Berckel BNM, Boellaard R, Veltman DJ. Organisers XXIInd
International Symposium on Cerebral Blood Flow, Metabolism, and Function & VIIth
Annual Report Nuclear Medicine & PET Research 2004-2005 26
International Conference on Quantification of Brain Function with PET, June 7-11, 2005,
2. Lammertsma AA. Co-organiser PET pharmacokinetic course 2005, June 12-14, 2005,
3. Boellaard R. Co-organiser NVKF workshop Acceptatietesten en kwaliteitscontrole van PET
4. Comans EF, Hoekstra OS. Organisers eight post-graduate courses on PET in oncology for
nuclear medicine physicians.
5. Comans EF, EF Smit, F Verzijlbergen, Hoekstra OS. Organisers NVALT national post-
graduate course on PET in lung cancer for pulmonologists, 2005, Ede, Netherlands.
6. De Jong HWAM. Co-organiser KLIFOP Fysicadag, November, 12, 2004, Rotterdam,
7. Windhorst AD. Co-organiser national radiochemistry collaborative workshop, Zelhem,
8. Windhorst AD, Lammertsma AA. Organisers LACDR Workshop PET in drug
development: feasibility, utility and prerequisites, November 21, 2005, Amsterdam,
iv. Editor or member editorial board international scientific journals
AA Geldof Journal of Cancer Research and Clinical Oncology (Editorial board)
JDM Herscheid Letters in Drug Design & Discovery (Editorial board)
OS Hoekstra The Oncologist (Section editor imaging)
AA Lammertsma NuklearMedizin (Section editor medical physics & radiation protection)
Journal of Cerebral Blood Flow and Metabolism (Deputy Chief-Editor)
Molecular Imaging and Biology (International associate editor)
European J of Nuclear Medicine and Molecular Imaging (Editorial board)
Current Medical Imaging Reviews (Editorial board)
Drug Discovery Today: Technologies (Guest editor)
v. Member national and international scientific organisations
-Member joint committee “Acceptatietesten en kwaliteitscontrole van PET camera’s”, Dutch
Society of Nuclear Medicine (NVNG) and Dutch Society of Clinical Physics (NVKF)
-Member quality registration committee Dutch Society for Medical Imaging and Radiotherapy
-Board member Dutch Society of Nuclear Medicine (NVNG)
-Board member Dutch Society for Oncology (NVVO)
-Member education renewal committee, Dutch Society of Nuclear Medicine (WEMONG,
Annual Report Nuclear Medicine & PET Research 2004-2005 27
-Board member Post Universitair Onderwijs Ziekenhuisapothekers (PUOZ)
-Board member Dutch Society of Nuclear Medicine (NVNG)
-Member Scientific Council, Leiden/Amsterdam Centre for Drug Research
-Member EORTC Translational research advisory committee (TRAC)
-Board member EORTC PAMM group
-Member ZON-MW VEMI (Vroege Evaluatie Medische Innovaties) committee
De Jong HWAM
-Board member Medical Physics Trainees (Klifop, NVKF)
-Member council, Dutch Society of Clinical Physics (Concilium, NVKF)
-Member educational committee, Dutch Society of Nuclear Medicine (OnderwijsCie, NVNG)
De Jong-Greuter CSM
-Member training committee Dutch Society for Medical Imaging and Radiotherapy (NVMBR)
-Member educational committee Dutch Society for Medical Imaging and Radiotherapy
-Director International Society for Cerebral Blood Flow and Metabolism
-Member IFAC BIOMED technical committee
-Board member Dutch Commission on Radiation Dosimetry (NCS)
-Board member Dutch Society of Clinical Physics (NVKF)
-Board member section nuclear medicine, Dutch Society of Clinical Physics (kring KFNG,
-Chairman Executive Committee for Board Registration, Dutch Society of Clinical Physics
Van Lingen A
-Member committee for scientific meetings, Dutch Society of Nuclear Medicine (NVNG)
-Member plenary visitation committee, Dutch Society of Nuclear Medicine (NVNG)
-Member Dutch working group “Advanced Drug Delivery/Drug Targeting” of the Netherlands
Society of Immunology, Netherlands Institute of Biology, and Netherlands Society for
-Chairman educational committee Dutch Society of Nuclear Medicine (OnderwijsCie, NVNG)
De Vries T
-Coordinator benchgroups nuclear medicine in the Netherlands (except eastern part of the
-Board member Radiochemie.nl
Annual Report Nuclear Medicine & PET Research 2004-2005 28
IX. Current trends and perspectives
i. Organisational structure
The reorganisation of the Department of Nuclear Medicine & PET Research, following its
formation in January 2004, was a lengthy process, requiring participation of all members of the
department. Functioning of a department, however, does not only depend on defining an
appropriate and functioning organisational structure, but more on the motivation of its members
to work together as a team. This will require constant attention in the coming years, especially as
the department is spread out over four different locations on the VU campus. This dispersion of
activities and people will further increase in 2006, as the installation of the PET/CT scanner
involves moving a large number of staff to another two locations. Clearly, this is far from ideal
for a multidisciplinary department, where communication between disiplines is extremely
important. The latter condition has been the main reason for forming sections, for appointing
section heads and coordinators within sections, and for setting up a meeting structure in which
there is regular discussion of progress, both within and between sections. These measures will
be monitored throughout the next year and, when appropriate, adjustments will be made. Based
on the general spirit after the new structure was in place, however, it is very unlikely that major
changes are needed. Nevertheless, it will be necessary to pursue better housing facilities for the
department, even if this can not be achieved in the near future, because of the general housing
problems of VUmc.
As mentioned earlier, the department created a new chair in radiopharmacochemistry in
collaboration with the Faculty of Sciences and BV Cyclotron VU. Unfortunately, the search for
an appropriate candidate for this post was not successful. Continuity of the work of the
chemistry section has been guaranteed by appointing prof. van Dongen as acting head of section.
This is, however, a temporary solution and the search for an appropriate candidate will be
initiated again in about two years time.
ii. Patient care
In 2006, the negotiations for setting up a nuclear medicine facility in the Amstelland Hospital,
Amstelveen will be finalised, and it is expected that this service will be opened early 2007. This
site will be run by the department of Nuclear Medicine & PET Research. This initiative is in line
with a general agreement of collaboration between the two hospitals.
The Cancer Centre Amsterdam (especially upon the instigation of prof. HM Pinedo) has made it
possible for the department to purchase a state-of-the-art PET-CT scanner. Prolonged
procedures proved necessary to allocate appropriate housing facilities within the VUmc site of
the department. Initially, this scanner should have been installed sometime in 2005. However,
as mentioned, space allocation problems were considerable, as its installation required not only
moving offices and laboratories, but also reenforcing the floor of the projected PET-CT room
floor of the hospital). At present, it is expected that installation will take place at the end of
It is foreseen that PET-CT is the first of an array of new technological developments aimed at
improving science as well as patient management, often by combining the best of the different
domains of diagnostic medicine. As such, academic centres are excellent laboratories for
exploration of the multidisciplinary interaction that should be the basis for real progress.
Therefore, at the VUmc, PET-CT is likely to intensify the bonds between radiology, nuclear
medicine & PET research and radiotherapy. These three departments also have in common that
Annual Report Nuclear Medicine & PET Research 2004-2005 29
they use radioactivity in a setting of advanced and expensive equipment, and that they participate
in a shared technologist training programme.
iii. Education and professional training
It is foreseen that PET(-CT) is rapidly diffusing throughout the Netherlands, with an estimated
number of scanners of one per 500.000 inhabitants by 2007. Experience obtained with the
technology assessment program (2000-present), the generally acknowledged lack of training
facilities within The Netherlands, and the very positive feedback of the participants who have
followed one of the post-graduate courses organised by the department, have been the main
reasons for extending the post-graduate teaching programme. This will be carried out in close
collaboration with others (VUmc medical specialists and third parties).
There is growing recognition that PET can play an important role in drug development, as it is
able to demonstrate efficacy of therapy in a non-invasive manner. At present, there is growing
interest in defining the role of PET in both preclinical and clinical studies. As a result some large
pharmaceutical companies invest in their own PET centres or they seek strategic collaborations
with academic centres. The collaboration between academic PET centres and pharmaceutical
industries is by no means one-way traffic. Knowledge within pharmaceutical industries can be
an important factor in developing new PET tracers. The Department of Nuclear Medicine &
PET Research therefore has an open mind in the interaction with industry. In the years 2004
and 2005, the department had ongoing collaborations with a number of industries (e.g.
Boehringer Ingelheim, Tyco/Mallinckrodt, Johnson & Johnson, IBA Molecular, Schering,
Philips, Ablynx, Aventis, Macrocyclics and CPS Molecular Imaging) 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 in the development of methodology. Following the merger of RNC, Department of
Nuclear Medicine and PET project, this range of activities nicely fits within the present
multidisciplinary setting of the VUmc department of Nuclear Medicine & PET Research, and in
fact a number of projects are anticipated for the coming years. At the same time, the department
will also maintain a positive attitude towards collaboration with other academic centres of
excellence, in an attempt to make efficient use of the limited (worldwide) expertise and facilites
for quantitative PET.
Annual Report Nuclear Medicine & PET Research 2004-2005 30
The formation of sections was part of the reorganisation process. They came into force during
2005. To better illustrate the expertise of the members of staff, the list below shows a listing by
section. An asterisk denotes that the discipline does not constitute a formal section within the
department. On march 23rd
, 2005, Mrs. Ban Tony, MD, one of our nuclear medicine residents,
died after a prolonged illness. With her, we have lost a warm-hearted, appreciated and hard-
i. Heads of Department
Prof. O.S. Hoekstra, MD, PhD, clinical (from 1 September, 2004)
Prof. A.A. Lammertsma, PhD, research
Prof. G.J.J. Teule, MD, PhD, clinical (until 1 September, 2004)
ii. Scientific Staff
W.G.E. Direcks, MSc
M. van Gelder, BSc
A.A. Geldof, PhD
F.J.P.M. van Kan, MSc (until 1 October, 2004)
Prof. A.A. Lammertsma, PhD, section head
C.F.M. Molthoff, PhD, coordinator biology
N. Proost, BSc (from 1 April, 2005)
A.J. Airaksinen, PhD (until 1 January, 2005)
J. Brinkhorst, BSc (from 1 February, 2005)
Prof. G.A.M.S. van Dongen, PhD, section head (from 1 January, 2006)
J.L.H. Eersels, MSc
J.D.M. Herscheid, PhD, coordinator basic radiochemistry
P.J. Klein, BSc
R.P. Klok, BSc
G. Luurtsema, BSc, coordinator metabolite analysis
M.P.J. Mooijer, BSc
P.L.B. van Ophemert
R.C. Schuit, BSc
K. Takkenkamp, BSc
E.W. van Tilburg, PhD
J. Verbeek, BSc
R.T. Versteegh, BSc
G.W.M. Visser, PhD
A.D. Windhorst, PhD, coordinator PET tracer development and production
A. de Nooij
Annual Report Nuclear Medicine & PET Research 2004-2005 31
L.F. van Rooij, section head
R.P. van der Valk
Medicine (section diagnostics & therapy)
B.N.M. van Berckel, MD, PhD, coordinator neuroPET
E.F.I. Comans, MD, PhD, coordinator whole body PET
Prof. O.S. Hoekstra, MD, PhD, section head
H.J. Pijpers, MD, PhD, coordinator conventional nuclear medicine
P.G.H.M. Raijmakers, MD, PhD
J.C. Roos, MD, PhD (until 1 June, 2004)
Prof. G.J.J. Teule, MD, PhD (until 1 September, 2004)
A. van Schie, MD (fellow from 1 September, 2004)
Resident nuclear medicine physicians
M. Akarriou, MD (from 1 December, 2002)
C.J. Hoekstra, MD, PhD (until 1 October, 2005)
A.B. van Dijk, MD, (extension as part-time fellow until 1 May, 2005)
R.J. Kooistra, MD, (until 1 April, 2005)
S.N.F. Rizvi, MD, (from 1 January, 2005)
A. van Schie, MD (until 1 September, 2004)
S.A. Srbljin, MD, (from 1 November, 2004)
J. Tim, MD, (from 1 January, 2004)
B.N. Tony, MD, (†23 March, 2005)
I.A.C. Rutten-Vermeltfoort, MD (from 1 January, 2003)
N.R.L. Wagenaar, MD, (from 1 September 2004)
Nuclear Medicine Technology
S.C.M. van Balen, BSc, coordinator PET
N.M. Bruin, BSc
E. Guijt, BSc
C.S.M. de Jong-Greuter, BSc
F. Jongsma, BSc
R.H.A. Koopmans, BSc
J.H. van Mourik
G.D. Mulder, BSc
J.M.L.H. Versteeg-Fontein, BSc
T. de Vries, BSc, section head, coordinator conventional nuclear medicine
A.M. de Wildt, BSc
A.Beemster (from 16 February, 2004, until 9 September, 2004)
S. Brunke (from 9 February, 2004, until 3 April, 2004)
M.J. Hartman (until 31 January, 2004)
T. van Kassel (from 10 November, 2003, until 3 January, 2004)
A.A. van de Ruit (from 1 September, 2004, until 1 January, 2005)
M.D. van Santen (until 25 July, 2005)
R. Boellaard, PhD, coordinator PET physics
H.W.A.M. de Jongh, PhD
M.A. Kropholler. MSc
Annual Report Nuclear Medicine & PET Research 2004-2005 32
Prof. A.A. Lammertsma, PhD, section head
A. van Lingen, PhD, coordinator conventional nuclear medicine physics
M. Lubberink, PhD
C.T. Mesina, MSc (until 1 July, 2004)
M.M. Yaqub, MSc (from 19 February, 2004)
F.H.P. van Velden, MSc (from 1 December, 2005)
J. Emmering, MD
A. Schuitemaker, MD
Prof. D.J. Veltman, MD, PhD (psychiatrist)
J.M. Zijlstra-Baalbergen, MD (hematologist)
A.A.M. van der Veldt
Prof. J.J. Leysen, PhD (from 1 November, 2004)
E.J.F. Franssen, PharmD, PhD (until 1 June, 2004)
N.H. Hendrikse, PharmD, PhD (from 1 February, 2005)
C.H. Bakker (until 1 November, 2005)
C. Karga (until 1 October, 2004)
J.C.G. van der Kuij
A. van Lingen, PhD, head of operational office, chief radiation health officer
C.G.A. Mascini-Heres diddens
J.J. van Veluwen, acting head patient administration (from 1 October, 2005)
R.T. Versteegh, BSc
M.M. Wiegman, BSc, head radiation safety officer (RNC site)
iii. PhD students
PhD students are listed per research institute. As some projects had a link with both ICEN and
LACDR, they have been put together.
Where appropriate, collaboration with other departments or external institutes is indicated. The
following abbreviations are used:
AMC: Academic Medical Centre
UL: University of Leiden
UMCG: University Medical Centre Groningen
UMCU: University Medical Centre Utrecht
Finally, PhD students are divided into different categories:
A – graduation and work prepared at VUmc
B – graduation at VUmc, work prepared elsewhere
C – graduation elsewhere, work prepared at VUmc
D – graduation and most of the work performed elsewhere
Annual Report Nuclear Medicine & PET Research 2004-2005 33
ICEN & LACDR
1. L.I. Arwert (+endocrinology, cat A)
2. A.L. Bartels (+UMCG, cat D)
3. J.P. Bremmer (+UMCU, cat D)
4. H. Folkersma (+neurosurgery, cat A)
5. S.G. Geuze (+UMCU, cat C/D)
6. O.A. van den Heuvel (+psychiatry, cat A)
7. U.M.H. Klumpers (+psychiatry, cat A)
8. M.A. Kropholler (cat A)
9. L.C. Liefaard (+UL, cat C/D)
10. G. Luurtsema (cat A)
11. M.L. van der Meer (+neurology, cat A)
12. C.T. Mesina (cat A)
13. M.M. Ponsen (+neurology, cat A)
14. A. Schuitemaker (+neurology, cat A)
15. N. Tolboom (+neurology, cat A)
16. F.H.P. van Velden (cat A)
17. N.C.C. Vulink (+UMCU, cat C/D)
18. S.P.A. Wolfensberger (+psychiatry, cat A)
19. M.M. Yaqub (cat A)
1. P. Borjesson (+otolaryngology, cat A)
2. J. Brouwer (+otolaryngology, cat A)
3. W.G.E. Direcks (cat A)
4. E.H. Elzinga (+rheumatology, cat A)
5. J. Emmering (+medical oncology, cat A)
6. G.J.M. Herder (+pulmonology; cat A)
7. J.J.M. van der Hoeven (cat A)
8. L. Hooft (+clinical epidemiology&biostatistics, cat A)
9. B.M. Klabbers (+radiotherapy, cat A)
10. N.C. Krak (+medical oncology, cat A)
11. A.J. de Langen (+pulmonology/surgery, cat A)
12. U. Joshi (cat A)
13. J.M.T. Omloo (+AMC, cat D)
14. L. van der Putten (+otolaryngology, cat A)
15. A. Senft (+otolaryngology, cat A)
16. H. van Tinteren (+clinical epidemiology&biostatistics, cat A)
17. O.J. Visser (+haematology, cat A)
18. M.J. Vos (+neurology, cat A)
19. M. Westerterp (+AMC, cat D)
20. M. van Wondergem (+haematology, cat A)
21. J.M. Zijlstra-Baalbergen (+hematology; cat A)
1. P.A. Dijkmans (+cardiology, cat A)
2. T. Hendriks (+cardiology, cat C/D)
3. P. Knaapen (+cardiology, cat A)
4. A. Rijbroek (+surgery, cat A)
5. L.J. Rijzewijk (+endocrinology, cat A)
Annual Report Nuclear Medicine & PET Research 2004-2005 34
6. I.A.C. Vermeltfoort (cat A)
7. M. Vervloet (+nephrology, cat A)
8. A. van der Weerdt (+cardiology, cat A)
1. O.P.P. Temmerman (+orthopaedics, cat A)
2. F. Vermaat (+surgery, cat A)
Annual Report Nuclear Medicine & PET Research 2004-2005 35
2004: JJM van der Hoeven. Prospects for positron emission tomography in the staging and
treatment of breast cancer patients. (Co-) promotors Prof Dr GJJ Teule, Prof Dr S Meijer, Dr
OS Hoekstra (cat A).
2005: MJ Vos. Evaluation of response, toxicity and outcome in glioma therapy. (Co-) promotors
Prof Dr JJ Heimans, Prof Dr W Vandertop, Dr Tj Postma, Dr OS Hoekstra (cat A).
2005: L Hooft. Molecular imaging in rare diseases: the case of thyroid cancer and positron
emission tomography. Print Partners Ipskamp, Amsterdam. 143 p. ISBN 90-9019542-4. (Co-)
promotors: Prof dr M Boers, Prof dr GJJ Teule, Dr OS Hoekstra, Dr MW van Tulder (cat A).
2005: OA van den Heuvel. Neuroimaging in obsessive-compulsive and related disorders:
investigation of the frontal-striatal and limbic circuits. (Co-) promotors Prof Dr R van Dyck,
Prof Dr AA Lammertsma, Dr HJ Groenewegen, Dr DJ Veltman (cat A). cum laude
ii. International peer reviewed papers
Admiraal GC, Schie van A, Meyel van JJM, Vasmel WLE. Giant Liver Hemangioma in 3 sisters.
J Gastroenterol Hepatol 2004; 19:344-345.
Annema JT, Hoekstra OS, Smit EF, Veselic M, Versteegh MI, Rabe KF. Towards a minimally
invasive staging strategy in NSCLC: analysis of PET positive mediastinal lesions by EUS-FNA.
Lung Cancer 2004; 44:53-60.
Arwert L, Roos JC, Lips P, Twisk JWR, Manoliu RA, Drent ML. Effects of 10 years of growth
hormone (GH) replacement therapy in adult GH-deficient men. Clin Endocrinol (Oxf) 2005;
Arwert LI, Veltman DJ, Deijen JB, Lammertsma AA, Jonker C, Drent ML. Memory
Performance and the Growth Hormone/Insulin-Like Growth Factor Axis in Elderly: A Positron
Emission Tomography Study. Neuroendocrinology 2005; 81:31-40.
Bipat S, van Leeuwen MS, Comans EF, Pijl ME, Bossuyt PM, Zwinderman AH, Stoker J.
Colorectal liver metastases: CT, MR imaging, and PET for diagnosis - meta-analysis. Radiology
Blokhuis TJ, van der Schaaf MC, van den Tol MP, Comans EF, Manoliu RA, van der Sijp JR.
Results of radio frequency ablation of primary and secondary liver tumors: long-term follow-up
with computed tomography and positron emission tomography-18
scanning. Scand J Gastroenterol Suppl 2004; 241:93-97.
Boellaard R, Krak NC, Hoekstra OS, Lammertsma AA. Effects of noise, image resolution,
and ROI definition on the accuracy of standard uptake values: a simulation study. J Nucl Med
Annual Report Nuclear Medicine & PET Research 2004-2005 36
Boellaard R, van Lingen A, van Balen SC, Lammertsma AA. Optimization of attenuation
correction for positron emission tomography studies of thorax and pelvis using count-based
transmission scans. Phys Med Biol 2004; 21; 49:N31-N38.
Boellaard R, Knaapen P, Rijbroek A, Luurtsema GJ, Lammertsma AA. Evaluation of basis
function and linear least squares methods for generating parametric blood flow images using 15
water and positron emission tomography. Mol Imaging Biol 2005; 7:273-285.
Börjesson P, Postema E, de Bree R, Roos JC, Leemans C, Kairemo K, van Dongen G.
Radioimmunodetection and radioimmunotherapy of head and neck cancer. Oral Oncol 2004;
Borst GR, Belderbos JS, Boellaard R, Comans EF, De Jaeger K, Lammertsma AA, Lebesque
JV. Standardised FDG uptake: a prognostic factor for inoperable non-small cell lung cancer.
Eur J Cancer 2005; 41:1533-1541.
Bravenboer N, Holzmann PJ, ter Maaten JC, Stuurman LM, Roos JC, Lips P. Effect of long-
term growth hormone treatment on bone mass and bone metabolism in growth hormone-
deficient men. Bone Miner Res 2005; 20:1778-1784.
Brouwer J, Bodar EJ, De Bree R, Langendijk JA, Castelijns JA, Hoekstra OS, Leemans CR.
Detecting recurrent laryngeal carcinoma after radiotherapy: room for improvement. Eur Arch
Otorhinolaryngol 2004; 261:417-422.
Brouwer J, de Bree R, Comans EF, Castelijns JA, Hoekstra OS, Leemans CR. 18
FDG PET in
the clinically negative neck: is it likely to be superior? Eur Arch Otorhinolaryngol 2004; 261:479-
Brouwer J, de Bree R, Hoekstra OS, Golding RP, Langendijk JA, Castelijns JA, Leemans CR.
Screening for distant metastases in patients with head and neck cancer: is chest computed
tomography sufficient? Laryngoscope 2005; 115:1813-1817.
Brouwer J, Bree R, Hoekstra OS, Langendijk JA, Castelijns JA, Leemans CR. Screening for
distant metastases in patients with head and neck cancer: what is the current clinical practice?
Clin Otolaryngol 2005; 30:438-443.
Van Dongen GA, Visser GW, Vrouenraets MB. Photosensitizer-antibody conjugates for
detection and therapy of cancer. Adv Drug Deliv Rev 2004; 56:31-52.
Eersels JL, Klok RP, Verbeek J, Jonker AJ, Herscheid JD. Synthesis and evaluation of
radiolabeled analogs of the antidepressant drug zimelidine as potential SPECT-ligands for the
serotonin transporter. Nucl Med Biol 2004; 31:563-569.
Eersels JLH, Travis MJ, Herscheid JDM. Manufacturing I-123 labelled radiopharmaceuticals.
Pitfalls and solutions. J Label Compd Radiopharm 2005; 48:241-257.
Engelbregt MJ, van Weissenbruch MM, Lips P, van Lingen A, Roos JC, Delemarre-van de
Waal HA. Body composition and bone measurements in intra-uterine growth retarded and early
postnatally undernourished male and female rats at the age of 6 months: comparison with
puberty. Bone 2004; 34:180-186.
Annual Report Nuclear Medicine & PET Research 2004-2005 37
Fabry HF, Mutsaers PG, Meijer S, Torrenga H, Pijpers R, van Leeuwen PAM, van der Sijp J.
Clinical relevance of parasternal uptake in sentinel node procedure for breast cancer. J Surg
Oncol 2004; 87:13-18.
De Geus-Oei LF, van Eerd-Vismale J, Molthoff C, Corstens F, Oyen W, Boerman O. Tracers
to monitor the response to chemotherapy: in vitro screening of four radiopharmaceuticals.
Cancer Biother Radiopharm 2004; 19:457-465.
Greuter HN, van Ophemert PL, Luurtsema G, Franssen EJ, Boellaard R, Lammertsma
AA. Validation of a multiwell gamma-counter for measuring high-pressure liquid
chromatography metabolite profiles. J Nucl Med Technol 2004; 32:28-32.
Greuter HJNM, van Ophemert PLB, Luurtsema G, van Berckel BNM, Franssen EJF,
Windhorst AD, Lammertsma AA. Optimizing an online SPE-HPLC method for analysis of
C]PK11195] and its metabolites in man. Nucl Med Biol 2005; 32:307-312.
Herder GJ, Golding RP, Hoekstra OS, Comans EF, Teule GJ, Postmus PE, Smit EF. The
performance of 18F-fluorodeoxyglucose positron emission tomography in small solitary
pulmonary nodules. Eur J Nucl Med Mol Imaging 2004; 31:1231-1236.
Herder GJ, van Tinteren H, Golding RP, Kostense PJ, Comans EF, Smit EF, Hoekstra OS.
Clinical prediction model to characterize pulmonary nodules: validation and added value of 18
fluorodeoxyglucose positron emission tomography. Chest 2005; 128:2490-2496.
Van den Heuvel OA, Veltman DJ, Groenewegen HJ, Dolan RJ, Cath DC, Boellaard R,
Mesina CT, van Balkom AJ, van Oppen P, Witter MP, Lammertsma AA, van Dyck R.
Amygdala activity in obsessive-compulsive disorder with contamination fear: a study with
oxygen-15 water positron emission tomography. Psychiatry Res 2004; 132:225-237.
Hoekstra CJ, Stroobants SG, Smit EF, Vansteenkiste J, van Tinteren H, Postmus PE, Golding
RP, Biesma B, Schramel FJ, van Zandwijk N, Lammertsma AA, Hoekstra OS. 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 2005;
Van der Hoeven JJ, Krak NC, Hoekstra OS, Comans EF, Boom RP, van Geldere D, Meijer S,
van der WE, Buter J, Pinedo HM, Teule GJ, Lammertsma AA. 18
glucose positron emission tomography in staging of locally advanced breast cancer. J Clin Oncol
Hofman HA, Knaapen P, Boellaard R, Bondarenko O, Gotte MJ, van Dockum WG, Visser
CA, van Rossum AC, Lammertsma AA, Visser FC. 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 2005; 12:639-44.
Hooft L, Hoekstra OS, Boers M, van Tulder MW, Van Diest P, Lips P. Practice, efficacy, and
costs of thyroid nodule evaluation: a retrospective study in a Dutch university hospital. Thyroid
Annual Report Nuclear Medicine & PET Research 2004-2005 38
Hooft L, van der Veldt AA, van Diest PJ, Hoekstra OS, Berkhof J, Teule GJ, Molthoff CF.
F]fluorodeoxyglucose uptake in recurrent thyroid cancer is related to hexokinase I expression
in the primary tumor. J Clin Endocrinol Metab 2005; 90:328-334.
De Jong HWAM, Boellaard R, Lenox M, Michel C, Lammertsma AA. Correction for
emission contamination in transmission scans for the High Resolution Research Tomograph.
IEEE Trans Nuclear Science, 2004; 51:673-676.
Joshi U, Hoekstra OS, Boellaard R, Comans EF, Raijmakers PG, Pijpers RJ, Miller SD,
Teule GJ, van Lingen A. Initial experience with a prototype dual-crystal (LSO/NaI) dual-head
coincidence camera in oncology. Eur J Nucl Med Mol Imaging 2004; 31:596-598.
Joshi U, van der Hoeven JJ, Comans EF, Herder GJ, Teule GJ, Hoekstra OS. In search of an
unknown primary tumour presenting with extracervical metastases: the diagnostic performance
of FDG-PET. Br J Radiol 2004; 77:1000-1006.
Joshi U, Raijmakers PG, van Lingen A, Comans EF, Pijpers R, Teule GJ, Hoekstra OS.
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 2005;
Joshi U, van der Sluijs JA, Teule GJ, Pijpers R. Proteus syndrome: a rare cause of
hemihypertrophy and macrodactyly on bone scanning. Clin Nucl Med 2005; 30:604-605.
Kessels LW, Simsek S, Van Hattum AH, Stam F, Comans EF. Nodular fasciitis: an unexpected
finding on computed tomography and positron emission tomography. Eur J Intern Med 2004;
Knaapen P, Boellaard R, Gotte MJ, Dijkmans PA, van Campen LM, de Cock CC, Luurtsema
G, Visser CA, Lammertsma AA, Visser FC. Perfusable tissue index as a potential marker of
fibrosis in patients with idiopathic dilated cardiomyopathy. J Nucl Med 2004; 45:1299-1304.
Knaapen P, van Campen LM, de Cock CC, Gotte MJ, Visser CA, Lammertsma AA, Visser, FC.
Effects of cardiac resynchronization therapy on myocardial perfusion reserve. Circulation 2004;
Knaapen P, van Dockum WG, Bondarenko O, Kok WE, Gotte MJ, Boellaard R, Beek AM,
Visser CA, van Rossum AC, Lammertsma AA, Visser FC. Delayed contrast enhancement and
perfusable tissue index in hypertrophic cardiomyopathy: comparison between cardiac MRI and
PET. J Nucl Med 2005; 46:923-9.
Knaapen P, Götte MJW, van Dijk J, de Cock CC, Allaart CP, Lammertsma AA, Visser FC.
Cardiac resynchronization therapy: assessment of dyssynchrony and effects on metabolism.
Future Cardiol 2005; 1:1-11.
Knaapen P, Lammertsma AA, Visser FC. Enhancement of perfusion reserve by cardiac
resynchronization therapy. Eur Heart J 2005; 26:1447-1448.
Krak NC, Hoekstra OS, Lammertsma AA. Measuring response to chemotherapy in locally
advanced breast cancer: methodological considerations. Eur J Nucl Med Mol Imaging 2004;
Annual Report Nuclear Medicine & PET Research 2004-2005 39
Krak NC, Boellaard R, Hoekstra OS, Twisk JW, Hoekstra CJ, Lammertsma AA. Effects of
ROI definition and reconstruction method on quantitative outcome and applicability in a
response monitoring trial. Eur J Nucl Med Mol Imaging 2005; 32:294-301.
Kropholler MA, Boellaard R, Schuitemaker A, van Berckel BN, Luurtsema G, Windhorst
AD, Lammertsma AA. Development of a tracer kinetic plasma input model for (R)-
[11C]PK11195 brain studies. J Cereb Blood Flow Metab 2005; 25:842-851.
Liefaard LC, Ploeger BA, Molthoff CF, Boellaard R, Lammertsma AA, Danhof M, Voskuyl
RA. Population pharmacokinetic analysis for simultaneous determination of Bmax and KD in vivo
by positron emission tomography. Mol Imaging Biol 2005; 18:1-11.
Lodder MC, Lems WF, Ader HJ, Marthinsen AE, van Coeverden SCCM, Lips P, Netelenbos JC,
Dijkmans BAC, Roos JC. Reproducibility of bone mineral density measurement in daily
practice. Ann Rheum Dis 2004; 63:285-289.
Lubberink M, Boellaard R, Van der Weerdt AP, Visser FC, Lammertsma AA. Quantitative
comparison of AW-OSEM and FBP reconstruction in 2D and 3D dynamic cardiac 18
PET. J Nucl Med 2004; 45:2008-2015.
Luurtsema G, de Lange EC, Lammertsma AA, Franssen EJ. Transport across the blood-
brain barrier: stereoselectivity and PET-tracers. Mol Imaging Biol 2004; 6:306-318.
Luurtsema G, Molthoff C, Schuit R, Windhorst A, Lammertsma A, Franssen E.
Evaluation of R-[11C]-verapamil as PET tracer of P-glycoprotein function in the blood–brain
barrier: kinetics and metabolism in the rat. Nucl Med Biol 2005; 32: 87-93.
Mey M van der, Janssen CG, Janssens FE, Jurzak M, Langlois X, Sommen FM, Verreet B,
Windhorst AD, Leysen JE, Herscheid JDM. Synthesis and biodistribution of [11
promising PET ligand for central NK1 receptors. Bioorg Med Chem 2005; 13:1579–1586.
Mijnhout GS, Riphagen II, Hoekstra OS. Update of the FDG PET search strategy. Nucl Med
Commun 2004; 25:1187-1189.
Moll AC, Hoekstra OS, Imhof SM, Comans EF, Schouten-van Meeteren AY, van der Valk P,
Boers M. Fluorine-18 fluorodeoxyglucose positron emission tomography (PET) to detect vital
retinoblastoma in the eye: preliminary experience. Ophthalmic Genet 2004; 25:31-35.
Nieuwenhuis EJ, van der Waal I, Leemans CR, Kummer A, Pijpers R, Castelijns JA, Brakenhoff
RH, Snow GB. Histopathologic validation of the sentinel node concept in oral and
oropharyngeal squamous cell carcinoma. Head Neck 2005; 27:150-158.
Noske DP, Peerdeman SM, Comans EF, Dirven CM, Knol DL, Girbes AR, Vandertop WP.
Cerebral microdialysis and positron emission tomography after surgery for aneurysmal
subarachnoid hemorrhage in grade I patients. Surg Neurol 2005; 64:109-115.
Van Oost FJ, van der Hoeven JJ, Hoekstra OS, Voogd AC, Coebergh JW, Van De Poll-Franse
LV. Staging in patients with locoregionally recurrent breast cancer: current practice and
prospects for PET. Eur J Cancer 2004; 40:1545-1553.
Pasic A, Brokx HA, Comans EF, Herder GJ, Risse EK, Hoekstra OS, Postmus PE, Sutedja
TG. Detection and staging of preinvasive lesions and occult lung cancer in the central airways
Annual Report Nuclear Medicine & PET Research 2004-2005 40
with 18F-fluorodeoxyglucose positron emission tomography: a pilot study. Clin Cancer Res
Perk LR, Visser GWM, Vosjan MJWD, Stigter-van Walsum M, Tijink BM, Leemans CR, van
Dongen GAMS. 89
Zr as a PET surrogate radioisotope for scouting biodistribution of the
therapeutic radiometals 90
Y and 177
Lu in tumor-bearing nude mice after coupling to the
internalizing antibody cetuximab. J Nucl Med 2005; 46:1898-1906.
Pijpers R, Buist MR, van Lingen A, Dijkstra J, van Diest PJ, Teule GJJ, Kenemans P,
Verheijen RHM. The sentinel node in cervical cancer: scintigraphy and laparoscopic gamma
probe-guided biopsy. Eur J Nucl Med Mol Imaging 2004; 31:1479-1486.
Van Rij CM, Huitema ADR, Swart EL, Greuter HNJM, Lammertsma AA, van Loenen AC,
Franssen EJF. Population plasma pharmacokinetics of 11
C-flumazenil at tracer concentrations.
Br J Clin Pharmacol 2005; 60:477-85.
Van Royen BJ, Baayen JC, Pijpers R, Noske DP, Schakenraad D, Wuisman PI. Osteoid
osteoma of the spine: a novel technique using combined computer-assisted and gamma probe-
guided high-speed intralesional drill excision. Spine 2005; 30:369-373.
Schins A, Van Kroonenburgh M, van Laere K, D'Haenen H, Lousberg R, Crijns H, Eersels J,
Honig A. Increased cerebral serotonin-2A receptor binding in depressed patients with
myocardial infarction. Psychiatry Research: Neuroimaging 2005; 139:155-163.
Sminia P, Kuipers G, Geldof A, Lafleur V, Slotman B. COX-2 inhibitors act as radiosensitizer
in tumor treatment. Biomed Pharmacother 2005; 59, Suppl 2:S272-S275.
Sturkenboom M, Franssen E, Berkhof J, Hoekstra OS. Physiological uptake of 18
in the neck and upper chest region: are there predictive characteristics? Nucl Med Commun
Temmerman OPP, Raijmakers PG, David EF, Pijpers R, Molenaar MA, Hoekstra OS,
Berkhof J, Manoliu RA, Teule GJ, Heyligers IC. A comparison of radiographic and
scintigraphic techniques to assess aseptic loosening of the acetabular component in a total hip
replacement. J Bone Joint Surg Am 2004; 86:2456-2463.
Temmerman OPP, Heyligers IC, Teule GJ, Hoekstra OS, Raijmakers PG. The value of
contrast and subtraction arthrography in the assessment of aseptic loosening of total hip
prostheses: a meta-analysis. Eur J Radiol 2005; 56:113-119.
Temmerman OPP, Raijmakers PG, Hoekstra OS, Teule GJ, Berkhof J, Heyligers IC.
Accuracy of diagnostic imaging techniques in the diagnosis of aseptic loosening of the femoral
component of a hip prosthesis: a meta-analysis. J Bone Joint Surg Br 2005; 87(6):781-785.
Termaat MF, Raijmakers PG, Scholten HJ, Bakker FC, Patka P, Haarman HJ. The accuracy of
diagnostic imaging for the assessment of chronic osteomyelitis: a systematic review and meta-
analysis. J Bone Joint Surg Am 2005; 87:2464-2471.
Van Tilburg EW, Franssen EJF, van der Hoeven JJM, van der Meij M, Elshove D,
Lammertsma AA, Windhorst AD. Radiosynthesis of [11
C]Docetaxel. J Label Compd
Radiopharm 2004; 47:763-777.
Annual Report Nuclear Medicine & PET Research 2004-2005 41
Van Tinteren H, Hoekstra OS, Boers M. Do we need randomised trials to evaluate diagnostic
procedures? Eur J Nucl Med Mol Imaging 2004; 31:129-131.
Van Tinteren H, Smit EF, Hoekstra OS. FDG-PET in addition to conventional work-up in
non-small-cell lung cancer. J Clin Oncol 2005; 23:1591-1592.
Tony B, Vos MJ, Berkhof J, Postma TJ, van Lingen A, Heimans JJ, Hoekstra OS.
Interobserver variability in the semi-quantitative assessment of 201
Tl SPECT in cerebral gliomas.
Nucl Med Commun 2005; 26:45-48.
Torrenga H, Fabry H, van der Sijp J, van Diest PJ, Pijpers R, Meijer S. Omitting axillary lymph
node dissection in sentinel node negative breast cancer patients is safe: a long term follow-up
analysis. J Surg Oncol 2004; 88:4-7.
Veltman DJ, Tuinebreijer WE, Winkelman D, Lammertsma AA, Witter MP, Dolan RJ,
Emmelkamp PM. Neurophysiological correlates of habituation during exposure in spider
phobia. Psychiatry Res 2004; 132:149-158.
Verel I, Visser GW, Vosjan MJ, Finn R, Boellaard R, van Dongen GA. High-quality 124
labelled monoclonal antibodies for use as PET scouting agents prior to 131
Eur J Nucl Med Mol Imaging 2004; 31:1645-52.
Verel I, Visser GWM, van Dongen GAMS. The Promise of Immuno-PET in
Radioimmunotherapy. J Nucl Med 2005; 46:164S-171S.
Verheij J, van Lingen A, Raijmakers PG, Spijkstra JJ, Girbes AR, Jansen EK, van den Berg
FG, Groeneveld AB. Pulmonary abnormalities after cardiac surgery are better explained by
atelectasis than by increased permeability oedema. Acta Anaesthesiol Scand 2005; 49:1302-1310.
Verheij J, Raijmakers PG, van Lingen A, Groeneveld AB. Simple vs complex radionuclide
methods of assessing capillary protein permeability for diagnosing acute respiratory distress
syndrome. J Crit Care 2005; 20:162-171.
Vos MJ, Berkhof J, Postma TJ, Hoekstra OS, Barkhof F, Heimans JJ. Thallium-201 SPECT:
the optimal prediction of response in glioma therapy. Eur J Nucl Med Mol Imaging 2006;
Van der Weerdt AP, Boellaard R, Knaapen P, Visser CA, Lammertsma AA, Visser FC.
Postinjection transmission scanning in myocardial 18
F-FDG PET studies using both filtered
backprojection and iterative reconstruction. J Nucl Med 2004; 45:169-75.
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. Esophageal cancer: CT, endoscopic US,
and FDG PET for assessment of response to neoadjuvant therapy-systematic review. Radiology
Van Westreenen HL, Westerterp M, Jager PL, van Dullemen HM, Sloof GW, Comans EFI, van
Lanschot JJ, Wiggers T, Plukker JT. Synchronous Primary Neoplasms Detected on 18
PET in Staging of Patients with Esophageal Cancer. J Nucl Med 2005; 46:1321-1325.
Ten Wolde M, Hagen PJ, Macgillavry MR, Pollen IJ, Mairuhu AT, Koopman MM, Prins MH,
Hoekstra OS, Brandjes DP, Postmus PE, Buller HR. Non-invasive diagnostic work-up of
Annual Report Nuclear Medicine & PET Research 2004-2005 42
patients with clinically suspected pulmonary embolism; results of a management study. J
Thromb Haemost 2004; 2:1110-1117.
iii. International peer reviewed papers (external papers by members of staff)
Bart J, Dijkers ECF, Wegman TD, de Vries EGE, van der Graaf WTA, Groen HJM, Vaalburg
W, Willemsen ATM, Hendrikse NH. New positron emission tomography tracer [11
reveals P-glycoprotein modulation kinetics. Br J Pharmacol 2005; 145:1045-1051.
Bokulic T, Vastenhouw B, de Jong HWAM, Van Dongen AJ, Van Rijk PP, Beekman FJ. Monte
Carlo-based down-scatter correction of SPECT attenuation maps. Eur J Nucl Med Mol Imaging
Elsinga PH, Hendrikse NH, Bart J, van Waarde A, Vaalburg W. Positron emission
tomography studies on binding of central nervous system drugs and P-glycoprotein function in
the rodent brain. Mol Imaging Biol 2005; 7:37-44.
Hwang D, Narendran R, Huang Y, Slifstein M, Talbot P, Sudo Y, van Berckel BNM, Kegeles
LS, Martinez D, Laruelle M. Quantitative analysis of N-[11
in vivo binding in nonhuman primates. J Nucl Med 2004; 45:338-346.
Kortekaas R, van Oostrom JCH, Willemsen ATM, Bart J, Leenders KL, Hendrikse NH.
Blood-brain barrier dysfunction in Parkinsonian midbrain in vivo. Ann Neurol 2005; 57:176-
Lavreysen H, Pereira SN, Leysen JE, Langlois X, Lesage AS. Metabotropic glutamate 1
receptor distribution and occupancy in the rat brain: a quantitative autoradiographic study using
H]R214127. Neuropharmacology 2004; 46:609-619.
Lavreysen H, Willemoens T, Leysen JE, Lesage AS. Antagonist-induced supersensitivity of
mGlu1 receptor signalling in cerebellar granule cells. Eur J Neurosci 2005; 21:1610-1616.
Leysen JE. 5-HT2 receptors. Curr Drug Targets CNS Neurol Disord 2004; 3:11-26.
Lubberink M, Kosugi T, Schneider H, Ohba H, Bergstrom M. Non-stationary convolution
subtraction scatter correction with a dual-exponential scatter kernel for the Hamamatsu SHR-
7700 animal PET scanner. Phys Med Biol 2004; 49:833-42.
Pindon A, Van Hecke G, Josson K, Leysen JE, Jurzak M. Internalization of human 5-HT4a
and 5-HT4b receptors is splice variant dependent. Biosci Rep 2004; 24:215-223.
Razifar P, Lubberink M, Schneider H, Langström B, Bengtsson E, Bergström M. Non-
isotropic noise correlation in PET data reconstructed by FBP but not by OSEM demonstrated
using auto-correlation function. BMC Medical Imaging 2005; 5:3.
Sandström M, Tolmachev V, Kairemo K, Lundqvist H, Lubberink M. Performance of
coincidence imaging with long-lived positron emitters as an alternative to dedicated PET and
SPECT. Phys Med Biol 2004; 49:5419-5432.
Annual Report Nuclear Medicine & PET Research 2004-2005 43
Taymans JM, Kia HK, Claes R, Cruz C, Leysen J, Langlois X. Dopamine receptor-mediated
regulation of RGS2 and RGS4 mRNA differentially depends on ascending dopamine projections
and time. Eur J Neurosci 2004; 19:2249-2260.
Taymans JM, Cruz C, Lesage A, Leysen JE, Langlois X. MK-801 alters RGS2 levels and
adenylyl cyclase sensitivity in the rat striatum. Neuroreport 2005; 16:159-162.
Taymans JM, Kia HK, Groenewegen HJ, Leysen JE, Langlois X. Bilateral control of brain
activity by dopamine D1 receptors: evidence from induction patterns of regulator of G protein
signaling 2 and c-fos mRNA in D1-challenged hemiparkinsonian rats. Neuroscience 2005;
Vaalburg W, Hendrikse NH, Elsinga PH, Bart J, van Waarde A. P-gp activity and biological
response. Toxicol Appl Pharmacol 2005; 207:257-260.
iv. National peer reviewed papers
Becker A, van Agtmael MA, Comans EF, Voskuyl AE. Persistent fever in a patient with
Salmonella typhimurium gonarthritis. Ned Tijdschr Geneeskd 2005; 149:33-36.
Van Essenberg M, Luurtsema G, Lammertsma AA, Franssen EJF. Een spoortje radioactief
water: de productie en klinische toepassingen van H2
O-PET. Pharmaceutisch weekblad 2004;
Kuijpens JL, Verheij CD, Haak HR, Ribot JG, Hoekstra OS, Coebergh JW. Surgery and
I therapy in patients with differentiated thyroid carcinoma in the south-east of the
Netherlands, 1983-1996, compliance with the 1987 consensus guidelines. Ned Tijdschr
Geneeskd 2004; 148:1835-1836.
Visser OJ, Zijlstra JM, van Dongen GA, Huijgens PC. Radio-immunotherapy for B-cell non-
Hodgkin lymphoma. Ned Tijdschr Geneeskd 2005; 149:2324-2328.
Terwisscha van Scheltinga S, Meijer S, Cuesta MA, Pijpers R, Meijer GA, den Boer FC, van der
Sijp JRM. Schildwachtklierprocedure bij colorectale carcinomen: huidige stand van zaken. Ned
Tijdschr Oncol 2005; 2:43-48.
Torrenga H,van Diest PJ, van der Wall E, Pijpers R, van der Sijp JRM, Meijer S.
Gerandomiseerde studie ‘directe versus uitgestelde okselklierdissectie’ bij mammacarcinoom
patiënten met een positieve schildwachtklier. Ned Tijdschr Oncol 2004; 1:185-189.
v. Miscellaneous publications
Van Essenberg M, Luurtsema G, Lammertsma AA, Franssen EJF. Een spoortje radioactief
water: de productie en klinische toepassingen van [15
O]H2O-PET. Tijdschr v Nucl Geneesk
Jager PL, Hoekstra OS. Richtlijnen voor NSCLC. Tijdschr v Nucl Geneesk 2005; 27:22-35.
Annual Report Nuclear Medicine & PET Research 2004-2005 44
Haslinghuis-Bajan LM, Hoekstra OS. Positron emissie tomografie in de oncologie. IKR
bulletin zomer 2005.
Greuter HNJM, Boellaard R, van Lingen A, Franssen EJF, Lammertsma AA.
Measurement of [18
F]FDG concentrations in blood samples: comparision of direct calibration
and standard solution methods. Tijdschr v Nucl Geneesk 2005; 27:9-11.
Greuter HNJM, van Ophemert PLB, Luurtsema G, Franssen EJF, Boellaard R,
Lammertsma AA. Validation of a multiwell gamma-counter for measuring high pressure liquid
chromatography metabolite profiles. Tijdschr v Nucl Geneesk 2005; 27:57-60.
Regelink G, Pruim J, De Bree R, Van Der Laan BF, Hoekstra OS, Roodenburg JL. De rol van
FDG PET voor de diagnostiek van patienten met een halskliermetastase van een onbekende
primaire tumor. Ned Tijdschr v Oncol 2004; 1:49-53.
Hoekstra OS. De rol van positronemissietomografie in oncologie en hematologie. Oncollectie
Lammertsma AA. Nieuwe PET-mogelijkheden voor in vivo onderzoek bij de ziekte van
Alzheimer. Tijdschr v Nucl Geneesk 2004; 26:82-85.
Termaat MF, Blokhuis TJ, Raijmakers PGHM, de Lange-de Klerk ESM, Bakker FC, Patka P,
Haarman HJTM. Post-traumatic chronic osteomyelitis: a rare and problematic diagnosis?
Osteosynthesis and Trauma Care 2005; 13:183-186.
Termaat MF, Raijmakers PGHM, Bakker FC, Patka P, Haarman HJTM. The diagnostic value
of FDG-PET in patients with suspected chronic bone infection. Osteosynthesis and Trauma
Care 2005; 13:249-253.
Termaat MF, Scholten HJ, Raijmakers PGHM, Bakker FC, Patka P, Haarman HJTM. Clinical
cases of post-traumatic chronic osteomyelitis.A retrospective study. Osteosynthesis and Trauma
Care 2005; 13:113-117.
vi. Book chapters
Manoliu RA, Hoekstra OS, Teule GJJ. Beeldvormende diagnostiek. In: Interne Geneeskunde.
Ed. J van der Meer, 2005 (13e
druk); uitg Bohn Stafleu van Loghem.
Vansteenkiste J, Hoekstra OS, Stroobants S, Smit EF, Postmus PE. FDG PET in lung cancer.
In: Lung Cancer: principles and practice; Eds. HI Pass, DP Carbone, DH Johnson, JD Minna.
Philadelphia, Lippincott Williams & Wilkins (3rd
Boellaard R, Lubberink M, De Jong, H, Kropholler MA, Lammertsma AA. Application of
various iterative reconstruction methods for quantitative 3D dynamic brain PET studies. In:
2004 IEEE Medical Imaging Conference Record. IEEE, Piscataway, New Jersey, USA, 2004: