expertise by keralaguest


									June 11

 Expertise of the VUmc Department of Nuclear Medicine &
   PET Research and the BV Cyclotron VU, Amsterdam

The Department of Nuclear Medicine & PET Research of the VU University Medical
Centre (VUmc), together with the BV Cyclotron VU, provides a means to fully
develop radiopharmaceuticals for PET and SPECT in both animal and human studies.
Expertise ranges from radionuclide production, through new tracer development and
preclinical evaluation, to clinical use of new and existing tracers with highly qualified
specialists who operate in a truly multidisciplinary environment. The whole process
can be performed according to state-of-the-art GMP/GLP/GCP standards. In addition,
the departmental radiopharmaceutical research, development and production site
(Radionuclide Centre: RNC) was recently inspected by the Dutch Health Care
Inspectorate and is licensed to manufacture tracers for human use according to the
latest EU guidelines. This position paper provides an overview of current expertise,
noting that developments are ongoing.

Prof. dr. A.A. Lammertsma
Department of Nuclear Medicine & PET research
VU University Medical Centre
De Boelelaan 1115
1081 HV Amsterdam
The Netherlands

Overview of available tracers

Licensed PET radiopharmaceuticals:
      C labelled: flumazenil, PK11195, raclopride, verapamil, R116301, palmitate,
                   R107474, DASB, PIB
       F labelled: FDG, FLT, fluoride, FP--CIT, MPPF, FDDNP,proline
       O labelled: H2O, O2,, CO, CO2
In development:
      C labelled: docetaxel, WAY100635,deprenyl, methionine
       N labelled: N2
       F labelled: FAZA, fluoromethylcholine

Licensed SPECT radiopharmaceuticals:
       I labelled: R91150, iomazenil, hippuran, iodine, MIBG, -CIT
        Kr:        Generator

Monoclonal antibodies and peptides
Validated and universal procedures are in place for labeling antibodies and peptides
for pharmacokinetics/biodistribution studies (99mTc, 186Re, 123I, 125I, 131I, 111In, 177Lu),
SPECT imaging (99mTc, 186Re, 123I, 131I, 111In, 177Lu), PET imaging (68Ga, 89Zr, 124I)
and radioimmunotherapy (186Re, 131I, 177Lu, 90Y). In recent years more than 15
different radioimmunoconjugates have been produced for clinical evaluation, either in
house or at other institutes. Several R&D collaborations with biotech companies are
ongoing. All quality tests are in place: radiochemical purity, conjugate stability,
substitution ratio, antibody integrity, immunoreactivity, preclinical in vivo behavior,
sterility, pyrogenicity and immunogenicity.

Isotopes available from Cyclotron production:
  C, 15O, 18F, 123I, 124I, 88Zr, 89Zr, 81Rb/81mKr


The department collaborates with several research centres and opinion leaders in the
field of molecular imaging. The department is a preferred centre for Boehringer
Ingelheim, Tyco/Mallinckrodt, Johnson & Johnson, IBA Molecular, Schering, Philips,
Ablynx, Aventis, Macrocyclics and Novartis for, amongst others, the development
and application of molecular imaging. These cover the whole range of collaboration
possibilities, from a custom radiolabelling service to an interactive collaborative
approach to development of methodology.

Overview of available tracer kinetic models and data analysis procedures

General models and data analysis tools
Single tissue, two tissue (reversible and irreversible), reference tissue (Lammertsma),
steady state (Jones, Lammertsma) and linearised (Patlak, Logan, Blomqvist, Ichise)
models, spectral (Cunningham), cluster (Ashburner) and factor (Hermansen) analysis,
basis pursuit (Gunn), parametric imaging (linearisations, basis functions), metabolite
models, dose ranging studies, biological half-life studies

Tracer kinetic models for specific applications

Perfusion, perfusable tissue index, glucose metabolism, oxygen utilisation, fatty acid
metabolism, blood volume, haematocrit, integrity blood-brain barrier, P-glycoprotein
function, pH, osteoblast activity, TK1 activity, MAO-B activity, dopamine D2 and D1
receptors, dopamine transporters, central (GABAA) and peripheral benzodiazepine
receptors, serotonin 5-HT1A receptors, NK1 receptors

Overview of available methodologies and animal models

Several in vitro, in vivo and ex vivo techniques such as autoradiography, binding
studies, cell cultures, molecular biology techniques, FACScan analysis, enzyme
assays, (pretreated) biodistribution studies, animal PET, anesthaesia (both inhalation
and injection)

Animal species
Rats, mice, rabbits, minipigs, rhesus monkeys, transgenic mice, nude mice and rats

Animal models
Oncology: breast, cervical, head & neck, lung, prostate and colon cancer, glioma
Neurology: Parkinson’s disease, depression, neurotrauma, MS, epilepsy
Cardiology: minipigs
Other:      osteomyelitis

Overview of clinical studies

       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 (chemotherapy &

Staff and facilities

BV Cyclotron VU
  Philips AVF 30 cyclotron
  2 IBA 18/9 cyclotrons
  Fully equipped GMP hotlab for the commercial production of [18F]FDG, 81mKr
  and [123I] labelled products

   P.J. van der Jagt, PhD, General manager
   P.J. van Leuffen, Head production
   R. Mooij, Head cyclotron operations
   P.S. Kruijer, BSc, Head commercial production radiopharmaceuticals
   F. van Langevelde, PhD, Head isotope production research

Department of Nuclear Medicine & PET Research
   State-of-the-art whole body PET camera (HR+, CTI/Siemens)
   High resolution research PET camera (HRRT, CTI/Siemens)
   Time-of-flight PET/CT scanner to be installed November 2006
   Dedicated rodent PET scanner to be installed Spring 2007
   Medrad infusion system (controlled injections/infusions)
   Veenstra on-line blood withdrawal & detection systems
   RDS111 cyclotron (CTI)
   Oxygen-15 gas delivery system
   25 Separate type II labs for working with radioactive material
   GMP compliant hotlab with 6 hotcells
   3 research hotcells, 1 shielded fumehood
   Metabolite analysis lab
   Small animal housing facilities
   Multiple HPLC and GC systems
   Multiple gammacounters and betacounters
   Phosphor imager

Heads of Department
    Prof. O.S. Hoekstra, MD, PhD, clinical
    Prof. A.A. Lammertsma, PhD, research
PET Chemistry
    A.D. Windhorst, PhD
    D. Laan, BSc
    M.P.J. Mooijer, BSc
    P.J. Klein, BSc
    R.P. Klok, BSc
    A.Y. Rijnders, BSc
    R. van Kooij, BSc
    J.S. Schepers, BSc
Iodine chemistry (SPECT)

    J.D.M. Herscheid, PhD
    J.L.H. Eersels, MSc
    J. Verbeek, BSc
Monoclonal antibody labelling
    Prof. G.A.M.S. van Dongen, PhD
    G.W.M. Visser, PhD
Metabolite analysis
    G. Luurtsema, PhD
    H.N.J.M. Greuter, BSc
    R.C. Schuit, BSc
    K. Takkenkamp, BSc
    P. van Ophemert, BSc
    C.F.M. Molthoff, PhD
    A.A. Geldof, PhD
    N. Proost, BSc
Pharmacy, QA/QC
    N.H. Hendrikse, PharmD, PhD
    R.P. Klok, BSc
    A. van Lingen, PhD
    R. Boellaard, PhD
    M. Lubberink, PhD
    R. Kloet, BSc
Nuclear medicine
    E.F.I. Comans, MD, PhD
    B.N.M. van Berckel, MD, PhD
    P.Raijmakers, MD, PhD
    A van Schie, MD
    L.F. van Rooij
    F.P. Buijs
    J.F. Keus
    A. de Nooijer
    P. Schollema
    R.P. van der Valk
Health Physics
    A. van Lingen, PhD
    J. Boesten
    M. Wiegman
    T. Weijer
    N. Bock
    A. Kroonenberg-Kalwij
    J. van der Kuij
    G. Stolker-Bouknecht

Above list of staff excludes temporary staff employed on various grants. In addition,
some 30 to 40 PhD students perform their PhD research in the Department of Nuclear

Medicine & PET Research. Most clinical research studies are performed in close
collaboration with the respective clinical departments of the VUmc.

Recent publications (PET only; from 2004 onwards)

Airaksinen AJ, Jablonowski JA, van der Mey M, Barbier AJ, Klok RP, Verbeek J, Schuit R, Herscheid
JDM, Leysen JE, Carruthers NI, Lammertsma AA, Windhorst AD (in press) Radiosynthesis and
biodistribution of a histamine H3-receptor antagonist 4-[3-(4-piperidin-1-yl-but-1-ynyl)-[11C]benzyl]-
morpholine: evaluation of a potential PET ligand. Nucl Med Biol.

Annema JT, Hoekstra OS, Smit EF, Veselic M, Versteegh MI, Rabe KF (2004) Towards a minimally
invasive staging strategy in NSCLC: analysis of PET positive mediastinal lesions by EUS-FNA. Lung
Cancer 44: 53-60.

Arwert LI, Veltman DJ, Deijen JB, Lammertsma AA, Jonker C, Drent ML (2005) Cognitive
functioning and the growth hormone/insuline-like growth factor-I (GH/IGF-I) axis in elderly subjects: a
positron emission tomography study. Neuroendocrinology 81: 31-40.

Bax JJ, Beanlands RS, Klocke FJ, Knuuti J, Lammertsma AA, Schaefers MA, Schelbert HR, Von
Schulthess GK, Shaw LJ, Yang GZ, Camici PG (in press) Diagnostic and clinical perspectives of
fusion imaging in cardiology: Is the total greater than the sum of its parts? Heart.

Bipat S, van Leeuwen MS, Comans EF, Pijl ME, Bossuyt PM, Zwinderman AH, Stoker J (2005)
Colorectal liver metastases: CT, MR imaging, and PET for diagnosis--meta-analysis. Radiology 237:

Blok BFM, Groen J, Bosch JLHR, Veltman DJ, Lammertsma AA (in press) Different brain effects
during chronic and acute sacral neuromodulation in urge incontinent patients with implanted
neuromostimulators. Br J Urol.

Boellaard R, Knaapen P, Rijbroek B, Luurtsema G, Lammertsma AA (2005) Evaluation of basis
function and linear least squares methods for generating parametric blood flow images using 15O-water
and PET. Mol Im Biol 7: 273-285.

Boellaard R, Krak NC, Hoekstra OS, Lammertsma AA (2004) Effects of noise, image resolution and
ROI definition on the accuracy of standard uptake values: a simulation study. J Nucl Med 45: 1519-

Boellaard R, van Lingen A, van Balen SCM, Lammertsma AA (2004) Optimization of attenuation
correction for positron emission tomography studies of thorax and pelvis using count-based
transmission scans. Phys Med Biol 49: N31-N38.

Börjesson PKE, Jauw YWS, Boellaard R, de Bree R, Comans EFI, Roos JC, Castelijns JA, Vosjan
MJWD, Kummer JA, Leemans CR, Lammertsma AA, Van Dongen GAMS (2006) Performance of
immuno-positron emission tomography with zirconium-89-labeled chimeric monoclonal antibody U36
in the detection of lymph node metastases in head and neck cancer patients. Clin Cancer Res 12: 2133-

Borst GR, Belderbos JSA, Boellaard R, Comans EFI, de Jaeger KD, Lammertsma AA, Lebesque JV
(2005) Standardized FDG uptake: a prognostic factor for inoperable non-small cell lung cancer. Eur J
Canc 41: 1533-1541.

Brouwer J, de Bree R, Comans EF, Castelijns JA, Hoekstra OS, Leemans CR (2004) 18FDG PET in the
clinically negative neck: is it likely to be superior? Eur Arch Otorhinolaryngol 261: 479-483.

Brouwer J, de Bree R, Hoekstra OS, Golding RP, Langendijk JA, Castelijns JA, Leemans CR (2005)
Screening for distant metastases in patients with head and neck cancer: is chest computed tomography
sufficient? Laryngoscope 115: 1813-1817.

Brouwer J, de Bree R, Hoekstra OS, Langendijk JA, Castelijns JA, Leemans CR (2005) Screening for
distant metastases in patients with head and neck cancer: what is the current clinical practice? Clin
Otolaryngol 30: 438-443.

Brouwer J, Bodar EJ, de Bree R, Langendijk JA, Castelijns JA, Hoekstra OS, Leemans CR (2004)
Detecting recurrent laryngeal carcinoma after radiotherapy: room for improvement. Eur Arch
Otorhinolaryngol 261: 417-422.

Dijkmans PA, Knaapen P, Aiazian E, Visser CA, Lammertsma AA, Visser FC, Kamp O (2006)
Quantification of myocardial perfusion using intravenous myocardial contrast echocardiography in
healthy volunteers: comparison with positron emission tomography. J Am Soc Echocardiogr 19: 285-

Eersels JLH, Travis MJ, Herscheid JDM (2005) Manufacturing I-123 labelled radiopharmaceuticals.
Pitfalls and solutions. J Label Compd Radiopharm 48: 241-257.

Greuter HNJM, van Ophemert PLB, Luurtsema G, van Berckel BNM, Franssen EJF, Windhorst BD,
Lammertsma AA (2005) Optimizing an on-line SPE-HPLC method for analysis of [11C]1-(2-
chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide [(R)-PK11195] and its
metabolites in man. Nucl Med Biol 32: 307-312.

Greuter HNJM, van Ophemert PLB, Luurtsema G, Franssen EJF, Boellaard R, Lammertsma AA
(2004) Validation of a multiwell -counter for measuring high-pressure liquid chromatography
metabolite profiles. J Nucl Med Technol 32: 28-32.

Herder GJ, Golding RP, Hoekstra OS, Comans EF, Teule GJ, Postmus PE, Smit EF (2004) The
performance of (18)F-fluorodeoxyglucose positron emission tomography in small solitary pulmonary
nodules. Eur J Nucl Med Mol Imaging 31: 1231-1236.

Herder GJ, van Tinteren H, Golding RP, Kostense PJ, Comans EF, Smit EF, Hoekstra OS (2005)
Clinical prediction model to characterize pulmonary nodules: validation and added value of 18F-
fluorodeoxyglucose positron emission tomography. Chest 128: 2490-2496.

Van den Heuvel OA, Veltman DJ, Groenewegen HJ, Dolan RJ, Cath DC, Boellaard R, Mesina CT, van
Balkom AJLM, van Oppen P, Witter MP, Lammertsma AA, van Dyck R (2004) Amygdala activity in
obsessive-compulsive disorder with contamination fear: a study with oxygen-15 water positron
emission tomography. Psychiatry Res 132: 225-237.

Hoekstra CJ, Stroobants SG, Smit EF, Vansteenkiste J, van Tinteren H, Postmus PE, Golding RP,
Biesma B, Schramel FJHM, van Zandwijk N, Lammertsma AA, Hoekstra OS (2005) Prognostic
relevance of response evaluation using [18F]-2-fluoro-2-deoxy-D-glucose positron emission
tomography in patients with locally advanced non-small-cell lung cancer. J Clin Oncol 23: 8362-8370.

Van der Hoeven JJM, Krak NC, Hoekstra OS, Comans EFI, Boom RPA, van Geldere D, Meijer S, van
der Wall E, Buter J, Pinedo HM, Teule GJJ, Lammertsma AA (2004) 18F-2-fluoro-2-deoxy-D-glucose
positron emission tomography in staging of locally advanced breast cancer. J Clin Oncol 22: 1253-

Hofman HA, Knaapen P, Boellaard R, Bondarenko O, Götte MJW, van Dockum WG, Visser CA, van
Rossum AC, LammertsmaAA, Visser FC (2005) Measurement of left ventricular volumes and function
with O-15-labeled carbon monoxide gated positron emission tomography: comparison with magnetic
resonance imaging. J Nucl Cardiol 12: 639-644.

Hooft L, van der Veldt AA, van Diest PJ, Hoekstra OS, Berkhof J, Teule GJ, Molthoff CF (2005)
[18F]fluorodeoxyglucose uptake in recurrent thyroid cancer is related to hexokinase I expression in the
primary tumor. J Clin Endocrinol Metab 90: 328-334.

Hwang D, Narendran R, Huang Y, Slifstein M, Talbot P, Sudo Y, van Berckel BNM, Kegeles LS,
Martinez D, Laruelle M (2004) Quantitative analysis of N-[11C]propyl-norapomorphine ([11C]NPA) in
vivo binding in nonhuman primates. J Nucl Med 45: 338-346.

De Jong HWAM, Boellaard R, Lenox M, Michel C, Lammertsma AA (2004) Correction for emission
contamination in transmission scans for the High Resolution Research Tomograph. IEEE Trans Nucl
Sci 51: 673-676.

Joshi U, Hoekstra OS, Boellaard R, Comans EF, Raijmakers PG, Pijpers RJ, Miller SD, Teule GJ, van
Lingen A (2004) Initial experience with a prototype dual-crystal (LSO/NaI) dual-head coincidence
camera in oncology. Eur J Nucl Med Mol Imaging 31: 596-8.

Joshi U, van der Hoeven JJ, Comans EF, Herder GJ, Teule GJ, Hoekstra OS (2004) In search of an
unknown primary tumour presenting with extracervical metastases: the diagnostic performance of
FDG-PET. Br J Radiol 77: 1000-1006.

Joshi U, Raijmakers PG, van Lingen A, Comans EF, Pijpers R, Teule GJ, Hoekstra OS (2005)
Evaluation of pulmonary nodules: comparison of a prototype dual crystal (LSO/NAI) dual head
coincidence camera and full ring positron emission tomography (PET). Eur J Radiol 55: 250-254.

Klok RP, Klein PJ, Herscheid JDM, Windhorst AD (2006) High yielding and GMP compliant
synthesis of the dopamine transporter ligand FP--CIT. J Label Compd Radiopharm 49: 77-89.

Klok RP, Windhorst AD (in press) A general GC analysis method for the determination of residual
solvents in PET tracer formulations. Nucl Med Biol.

Knaapen P, Boellaard R, Götte MJW, Dijkmans PA, van Campen LMC, de Cock CC, Luurtsema G,
Visser CA, Lammertsma AA, Visser FC (2004) Perfusable tissue index as a potential marker of fibrosis
in patients with idiopathic dilated cardiomyopathy. J Nucl Med 45: 1299-1304.

Knaapen P, van Campen LM, de Cock CC, Götte MJ, Visser CA, Lammertsma AA, Visser FC (2004)
Effects of cardiac resynchronization therapy on myocardial perfusion reserve. Circulation 110: 646-

Knaapen P, van Dockum WG, Bondarenko O, Kok WEM, Götte MJW, Boellaard R, Beek AM, Visser
CA, van Rossum AC, Lammertsma AA, Visser FC (2005) Delayed contrast enhancement and
perfusable tissue index in hypertrophic cardiomyopathy: comparison between cardiac MRI and PET. J
Nucl Med 46: 923-929.

Knaapen P, Lammertsma AA, Visser FC (2005) Enhancement of perfusion reserve by cardiac
resynchronization therapy. Eur Heart J 26: 1447-1448.

Knaapen P, Bondarenko O, Beek AM, Götte MJW, Boellaard R, van der Weerdt AP, Visser CA, van
Rossum AC, Lammertsma AA, Visser FC (2006) Impact of scar on water-perfusable tissue index in
chronic ischemic heart disease: evaluation with PET and contrast-enhanced MRI. Mol Im Biol 8: 245-

Knaapen P, Götte MJW, Paulus WJ, Zwanenburg JJM, Dijkmans PA, Boellaard R, Marcus JT, Twisk
JWR, Visser CA, van Rossum AC, Lammertsma AA, Visser FC (2006) Does myocardial fibrosis
hinder contractile function and perfusion in idiopathic dilated cardiomyopathy? PET and MRI imaging
study. Radiology 240: 380-388.

Krak NC, Boellaard R, Hoekstra OS, Twisk JWR, Hoekstra CJ, Lammertsma AA (2005) Effects of
ROI definition and reconstruction method on quantitative outcome and applicability in a response
monitoring trial. Eur J Nucl Med Mol Imaging 32: 294-301.

Krak NC, Hoekstra OS, Lammertsma AA (2004) Measuring response to chemotherapy in locally
advanced breast cancer: methodological considerations. Eur J Nucl Med Mol Imaging 31: S103-S111.

Kropholler MA, Boellaard R, Schuitemaker A, van Berckel BNM, Luurtsema G, Windhorst AD,
Lammertsma AA (2005) Development of a tracer kinetic plasma input model for (R)-[11C]PK11195
brain studies. J Cereb Blood Flow Metab 25: 842-851.

Kropholler MA, Boellaard R, Schuitemaker A, Folkersma H, van Berckel BNM, Lammertsma AA (in
press) Evaluation of reference tissue models for the analysis of [ 11C](R)-PK11195 studies. J Cereb
Blood Flow Metab.

Lammertsma AA, Hoekstra CJ, Giaccone G, Hoekstra OS (2006) How should we analyse FDG PET
studies for monitoring tumour response? Eur J Nucl Med Mol Imaging 33, Suppl 1: S16-S21.

Liefaard LC, Ploeger BA, Molthoff CFM, Boellaard R, Lammertsma AA, Danhof M, Voskuyl RA
(2005) Population pharmacokinetic analysis for simultaneous determination of B max and KD in vivo by
positron emission tomography. Mol Im Biol 7: 411-421.

Luurtsema G, de Lange ECM, Lammertsma AA, Franssen EJF (2004) Transport across the blood-brain
barrier: stereoselectivity and PET-tracers. Mol Im Biol 6: 306-318.

Luurtsema G, Molthoff CFM, Schuit RC, Windhorst AD, Lammertsma AA, Franssen EJF (2005)
Evaluation of (R)-[11C]verapamil as PET tracer of P-glycoprotein function in the blood-brain barrier:
kinetics and metabolism in the rat. Nucl Med Biol 32: 87-93.

Lubberink M, Boellaard R, van der Weerdt AP, Visser FC, Lammertsma AA (2004) Quantitative
comparison of analytic and iterative reconstruction methods in 2- and 3-dimensional dynamic cardiac
   F-FDG PET. J Nucl Med 45: 2008-2015.

Lubberink M, Luurtsema G, van Berckel BNM, Boellaard R, Toornvliet JR, Windhorst AD, Franssen
EJF, Lammertsma AA (in press) Evaluation of a tracer kinetic models for quantification of P-
glycoprotein function using (R)-[11C]verapamil and PET. J Cereb Blood Flow Metabol.

Van der Meij M, Janssen CG, Janssens FE, Jurzak M, Langlois X, Sommen FM, Verreet B, Windhorst
AD, Leysen JE, Herscheid JDM (2005) Synthesis and biodistribution of [ 11C]R116301, a promising
PET ligand for central NK1 receptors. Bioorg Med Chem 13: 1579–1586.

Van der Meij M, Windhorst AD, Kennis L, Bisschof F, Klok RP, Bakker M, Langlois X, Heylen L,
Herscheid JDM, Jurzak M, Leysen JE (2006) Synthesis and in vivo studies of [11C]R107474, a new
radiolabeled 2-adrenoceptor antagonist. Bioorg Med Chem 14: 4526-4543.

Mijnhout GS, Riphagen II, Hoekstra OS (2004) Update of the FDG PET search strategy. Nucl Med
Commun 25: 1187-1189.

Moll AC, Hoekstra OS, Imhof SM, Comans EF, Schouten-van Meeteren AY, van der Valk P, Boers M
(2004) Fluorine-18 fluorodeoxyglucose positron emission tomography (PET) to detect vital
retinoblastoma in the eye: preliminary experience. Ophthalmic Genet 25: 31-35.

Nestor M, Persson M, van Dongen GAMS, Jensen HJ, Lundqvist H, Anniko M, Tolmachev V (2005)
In vitro evaluation of the astatinated chimeric monoclonal antibody U36, a potential candidate for
treatment of head and neck squamous cell carcinoma. Eur J Nucl Med Mol Imaging 32: 1296-1304.

Noske DP, Peerdeman SM, Comans EF, Dirven CM, Knol DL, Girbes AR, Vandertop WP (2005)
Cerebral microdialysis and positron emission tomography after surgery for aneurysmal subarachnoid
hemorrhage in grade I patients. Surg Neurol 64: 109-115.

Van Oost FJ, van der Hoeven JJ, Hoekstra OS, Voogd AC, Coebergh JW, Van De Poll-Franse LV
(2004) Staging in patients with locoregionally recurrent breast cancer: current practice and prospects
for PET. Eur J Cancer 40: 1545-1553.

Pasic A, Brokx HA, Comans EF, Herder GJ, Risse EK, Hoekstra OS, Postmus PE, Sutedja TG (2005)
Detection and staging of preinvasive lesions and occult lung cancer in the central airways with 18F-
fluorodeoxyglucose positron emission tomography: a pilot study. Clin Cancer Res 11: 6186-6189.

Perk LR, Visser GWM, Vosjan MJWD, Stigter-van Walsum M, Tijink BM, Leemans CR, van Dongen
GAMS (2005) Evaluation of 89Zr as a PET surrogate radioisotope for scouting the biodistribution of the
therapeutic radiometals 90Y and 177Lu in tumor bearing nude mice, after coupling to the internalizing
antibody cetuximab. J Nucl Med 46: 1998-1906.

Perk LR, Visser OJ, Stigter-van Walsum M, Vosjan MJWD, Visser GWM, Zijlstra JM, Huijgens PC,
van Dongen GAMS (in press) Preparation and evaluation of 89Zr-Zevalin for monitoring 90Y-Zevalin
biodistribution with positron emission tomography. Eur J Nucl Med Mol Imaging.

Van Rij CM, Huitema ADR, Swart EL, Greuter HNJM, Lammertsma AA, van Loenen AC, Franssen
EJF (2005) Population plasma pharmacokinetics of 11C-flumazenil at tracer concentrations. Br J Clin
Pharmacol 60: 477-485.

Rimoldi O, Schäfers KP, Boellaard R, Turkheimer F, Stegger L, Law MP, Lammertsma AA, Camici
PG (2006) Quantification of subendocardial and subepicardial blood flow using 15O-labeled water and
PET: experimental validation. J Nucl Med. 47: 163-172.

Shankar LK, Hoffman JM, Bacharach S, Graham MM, Karp J, Lammertsma AA, Larson S, Mankoff
DA, Siegel BA, van den Abbeele A, Yap J, Sullivan D (2006) Consensus recommendations for the use
of 18F-FDG as an indicator of therapeutic response in patients in national cancer institute trials. J Nucl
Med 47: 1059-1066.

Steenbakkers RJ, Duppen JC, Fitton I, Deurloo KE, Zijp LJ, Comans EF, Uitterhoeve AL, Rodrigus
PT, Kramer GW, Bussink J, De Jaeger K, Belderbos JS, Nowak PJ, van Herk M, Rasch CR (2006)
Reduction of observer variation using matched CT-PET for lung cancer delineation: a three-
dimensional analysis. Int J Radiat Oncol Biol Phys 64: 435-448.

Sturkenboom M, Franssen E, Berkhof J, Hoekstra OS (2004) Physiological uptake of 18FDG uptake in
the neck and upper chest region: are there predictive characteristics? Nucl Med Commun 25: 1109-

Tijink BM, Neri D, Leemans CR, Budde M, Berndorff D, Stigter-van Walsum M, Zardi L, van Dongen
GAMS (2006) Radioimmunotherapy of head and neck cancer xenografts using 131I-labeled antibody
L19-SIP for selective targeting of tumor vasculature. J Nucl Med 47: 1127-1135.

Toornvliet R, van Berckel BNM, Luurtsema G, Lubberink M, Geldof AA, Bosch TM, Oerlemans R,
Lammertsma AA, Franssen EJF (2006) Effect of age on functional P-glycoprotein in the blood brain
barrier measured using (R)- [11C]verapamil and positron emission tomography. Clin Pharmacol Ther
79: 540-548.

Van Tilburg EW, Franssen EJF, van der Hoeven JJM, van der Meij M, Elshove D, Lammertsma AA,
Windhorst AD (2004) Radiosynthesis of [11C]docetaxel. J Label Compd Radiopharm 47: 763-777.

Van Tilburg E, Windhorst AD, van der Meij M, Herscheid JDM (2006) One-pot synthesis of [11C]ureas
via triphenylphosphinimines. J Label Compd Radiopharm 49: 321-330.

Veltman DJ, Tuinebreijer WF, Winkelman D, Lammertsma AA, Witter MP, Dolan RJ, Emmelkamp
PMG (2004) Neurophysiological correlates of habituation during exposure in spider phobia. Psychiatry
Res 132: 149-158.

Verel I, Visser GW, Vosjan MJ, Finn R, Boellaard R, van Dongen GA (2004) High-quality 124I-
labelled monoclonal antibodies for use as PET scouting agents prior to 131I-radioimmunotherapy. Eur J
Nucl Med Mol Imaging 31: 1645-1652.

Verel I, Visser GWM, van Dongen GAMS (2005) The promise of immuno-PET in
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