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1. Short-Lived Positron Emitting Radionuclides

Author: A. M. J. Paans and W. Vaalburg
Subjects: Radionuclide, Positron, Radiochemistry, Environmental science
Published: 2019
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2. Synthesis and 11C-labelling of the ACTH fragment analogue H-Met(O2)-Glu-His-Phe-d-Lys-Phe-OH (Org 2766) via its homocystine-containing precursor

Author: Wpa Janssen, Psl Janssen, Pata Melgers, Jw Vannispen, W Vaalburg, and Jfga Jansen
Subjects: Stereochemistry, Dimer, Molecular Sequence Data, Methylation, Biochemistry, High-performance liquid chromatography, Peptide Fragments, Catalysis, Sulfone, Homocystine, chemistry.chemical_compound, Adrenocorticotropic Hormone, Anti-Anxiety Agents, chemistry, Phe-D-Lys-Phe, Labelling, Amino Acid Sequence, Radioactive Tracers
Abstract: The hexapeptide dimer (H-Hcy-Glu-His-Phe-D-Lys-Phe-OH)2 was synthesized using solution methods and characterized. Its conversion into H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH, Org 2766, was studied on a small scale in as short a time as possible; reduction of the disulfide bond using Na/NH3, reaction with CH3I, oxidation with H2O2 and catalyst and purification by HPLC were carried out starting with 2 mg of the dimer in a total preparation time of approximately 22 min, starting with the addition of CH3I. The preparation of the 11C-labelled analogue was carried out by methylation with 11CH3I. Restrictions imposed by working with carbon-11 will be discussed.
Published: 2009
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3. P-glycoprotein activity and biological response

Author: Philippus Elsinga, W Vaalburg, van Aren Waarde, NH Hendrikse, Joost Bart, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Targeted Gynaecologic Oncology (TARGON), and Clinical pharmacology and pharmacy
Subjects: Drug, media_common.quotation_subject, Drug Resistance, ATP-binding cassette transporter, Pharmacology, Toxicology, Radioligand Assay, Pharmacokinetics, Genetic, In vivo, Cyclosporin a, Animals, Humans, ATP Binding Cassette Transporter, Subfamily B, Member 1, Polymorphism, P-glycoprotein, media_common, Polymorphism, Genetic, biology, P-Glycoprotein, Drug Resistance, Multiple, Multiple drug resistance, Drug Resistance, Neoplasm, Positron-Emission Tomography, biology.protein, Neoplasm, Efflux, Multiple
Abstract: P-glycoprotein (P-gp) is a transmembrane drug efflux pump encoded by the MDR-1 gene in humans. Most likely P-gp protects organs against endogenous and exogenous toxins by extruding toxic compounds such as chemotherapeutics and other drugs. Many drugs are substrates for P-gp. Since P-gp is also expressed in the blood-brain barrier, P-gp substrates reach lower concentrations in the brain than in P-gp-negative tissues. Failure of response to chemotherapy of malignancies can be due to intrinsic or acquired drug resistance. Many tumors are multidrug resistant (MDR); resistant to several structurally unrelated chemotherapeutic agents. Several mechanisms are involved in MDR of which P-gp is studied most extensively. P-gp extrudes drugs out of tumor cells resulting in decreased intracellular drug concentrations, leading to the MDR phenotype. Furthermore, the MDR-1 gene exhibits several single nucleotide polymorphisms, some of which result in different transport capabilities. P-gp functionality and the effect of P-gp modulation on the pharmacokinetics of novel and established drugs can be studied in vivo by positron emission tomography (PET) using carbon-11 and fluorine-18-labeled P-gp substrates and modulators. PET may demonstrate the consequences of genetic differences on tissue pharmacokinetics. Inhibitors such as calcium-channel blockers (verapamil), cyclosporin A, ONT-093, and XR9576 can modulate the P-gp functionality. With PET the effect of P-gp modulation on the bioavailability of drugs can be investigated in humans in vivo. PET also allows the measurement of the efficacy of newly developed P-gp modulators.
Published: 2005
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4. [ 18 F]FHPG Positron Emission Tomography for Detection of Herpes Simplex Virus (HSV) in Experimental HSV Encephalitis

Author: AR Buursma, J Schirm, Hans Klein, W Vaalburg, J Garssen, Nanno Mulder, de Elisabeth G. E. Vries, D Kegler, Geesiena Hospers, van Aren Waarde, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE)
Subjects: Fluorine Radioisotopes, HERPES-SIMPLEX-VIRUS-1, Immunology, Herpesvirus 1, Human, DIAGNOSIS, medicine.disease_cause, Microbiology, Herpesviridae, Virus, Lesion, Virology, Alphaherpesvirinae, INFECTION, SCHIZOPHRENIA, medicine, Animals, Humans, Encephalitis, Viral, Ganciclovir, BRAIN-EDEMA, medicine.diagnostic_test, biology, Viral encephalitis, GENE-THERAPY, Brain, VIRAL ENCEPHALITIS, Herpes Simplex, INOCULATION, medicine.disease, biology.organism_classification, Rats, ALZHEIMERS-DISEASE, ACYCLOVIR, Herpes simplex virus, Positron emission tomography, Positron-Emission Tomography, Insect Science, Pathogenesis and Immunity, medicine.symptom, Encephalitis
Abstract: Herpes simplex virus type 1 (HSV-1) is one of the most common causes of sporadic encephalitis. The initial clinical course of HSV encephalitis (HSE) is highly variable, and the infection may be rapidly fatal. For effective treatment with antiviral medication, an early diagnosis of HSE is crucial. Subtle brain infections with HSV may be causally related to neuropsychiatric disorders such as Alzheimer's dementia. We investigated the feasibility of a noninvasive positron emission tomography (PET) imaging technique using [ 18 F]FHPG as a tracer for the detection of HSE. For this purpose, rats received HSV-1 (infected group) or phosphate-buffered saline (control group) by intranasal application, and dynamic PET scans were acquired. In addition, the distribution of tracer accumulation in specific brain areas was studied with phosphor storage imaging. The PET images revealed that the overall brain uptake of [ 18 F]FHPG was significantly higher for the infected group than for control animals. Phosphor storage images showed an enhanced accumulation of [ 18 F]FHPG in regions known to be affected after intranasal infection with HSV. High-performance liquid chromatography metabolite analysis showed phosphorylated metabolites of [ 18 F]FHPG in infected brains, proving that the increased [ 18 F]FHPG uptake in infected brains was due to HSV thymidine kinase-mediated trapping. Freeze lesion experiments showed that damage to the blood-brain barrier could in principle induce elevated [ 18 F]FHPG uptake, but this nonspecific tracer uptake could easily be discriminated from HSE-derived uptake by differences in the tracer kinetics. Our results show that [ 18 F]FHPG PET is a promising tool for the detection of HSV encephalitis.
Published: 2005
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5. Scintigraphic Imaging of HSVtk Expression in Gene Therapy

Author: E. F. J. de Vries, A. R. Buursma, and W Vaalburg
Subjects: Ganciclovir, Reporter gene, Genetic enhancement, Transgene, Transfection, Suicide gene, Biology, Molecular biology, Thymidine kinase, Drug Discovery, medicine, Molecular Medicine, Gene, medicine.drug
Abstract: Suicide gene therapy is under investigation as a treatment for cancer. In this therapy, a suicide gene is introduced into tumor cells, enabling the conversion of a prodrug into a toxic metabolite that selectively kills the transfected tumor cells. In the most investigated strategy, the herpes simplex virus thymidine kinase (HSVtk) suicide gene is used in combination with the prodrug ganciclovir. To assess the efficiency and safety of gene therapy protocols, a noninvasive method to assay the magnitude, kinetics and spatial distribution of transgene expression is essential. Imaging methods for repetitive monitoring of HSVtk transgene expression in living animals and humans, using single photon emission computed tomography (SPECT) or positron emission tomography (PET), have been developed. For many therapeutic genes, however, no imaging method is available. In these cases, reporter genes can be applied. Expression of the therapeutic gene can be determined indirectly by imaging a reporter gene, like HSVtk, that is linked to the therapeutic gene. Reporter genes can also be applied to monitor the expression of endogenous genes and to track the fate of transplanted cells. This paper presents an updated review on the progress in the field of non-invasive nuclear imaging of HSVtk transgene expression in gene therapy.
Published: 2005
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6. Evaluation of [18F]fluorinated sigma receptor ligands in the conscious monkey brain

Author: Hideo Tsukada, Philippus Elsinga, Tadayuki Kobayashi, W Vaalburg, Kazunori Kawamura, K. Ishiwata, Takeharu Kakiuchi, Yuichi Kimura, Norihiro Harada, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: Male, Fluorine Radioisotopes, medicine.medical_specialty, Consciousness, Sigma receptor, Striatum, Ligands, Binding, Competitive, BINDING-SITES, Piperazines, INCREASE, Cellular and Molecular Neuroscience, Thalamus, Cerebellum, Cerebellar hemisphere, Internal medicine, medicine, Haloperidol, Animals, Receptors, sigma, sigma receptor, Receptor, IN-VIVO, Brain Chemistry, Cerebral Cortex, Brain Mapping, Chemistry, Binding potential, NOREPINEPHRINE RELEASE, Human brain, Macaca mulatta, Corpus Striatum, PET, medicine.anatomical_structure, Endocrinology, Cerebral cortex, Anesthesia, PET LIGAND, fluorine-18, HIPPOCAMPUS, monkey, SA4503, Antipsychotic Agents, Tomography, Emission-Computed, medicine.drug
Abstract: PET-imaging of the sigma receptors is very helpful to understand processes, e.g., several central nervous system (CNS)-diseases in which the sigma receptors are involved. The [F-18]fluoroethylated analogs of SA4503 and SA5845 ([F-18]FE-SA4503 and [F-18]FE-SA5845) were evaluated in conscious monkeys to estimate its suitability for human application for PET. Conscious monkeys (Macaca Mulatta) were either scanned with [F-18]FE-SA4503 or [F-18]FE-SA5845 (n = 3 for both groups, 220 - 802 MBq). After a dynamic study of 120 min, radioactivity was displaced by intravenous (i.v.) injection of haloperidol (1 mg/kg). One month later the same set of three monkeys were scanned with [F-18]FE-SA4503 for 120 min and "cold" SA4503 (1 mg/kg) was infused to displace the radioactivity, and the other three monkeys were pretreated with haloperidol (1 mg/kg) before the 120-min PET-scan with [F-18]FE-SA5845. Cortical areas (cingulate, frontal, occipital, parietal, temporal), striatum, and thalamus showed high radioactivity uptake. Infusion of haloperidol displaced the radioactivity levels of the two radioligands. The same effect was found for [18F]FE-SA4503 after SA4503 displacement. Pretreatment with haloperidol blocked the [F-18]FE-SA5845 binding to give PET-images with low and uniform uptake in the brain. The findings demonstrated the reversible binding of the two radioligands. Metabolite analysis showed that 14% and 23% parent compound of [F-18]FE-SA5845 and [F-18]FE-SA4503, respectively, at 120 min postinjection was present in plasma. Kinetic analysis showed that the binding potential of [F-18]FE-SA5845 was higher in all brain regions than that of [F-18]FE-SA4503 (4.75-8.79 vs. 1.65-4.04). The highest binding potential was found in the hippocampus, followed by the cortical regions, thalamus, cerebellar hemisphere, striatum and vermis. Both [F-18]FE-SA compounds bound specifically to cerebral sigma receptors of the monkey and have potential for mapping sigma receptors in the human brain. (C) 2004 Wiley-Liss, Inc.
Published: 2004
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7. C-Choline Positron Emission Tomography for the Evaluation after Treatment of Localized Prostate Cancer

Author: Jan Pruim, Hja Mensink, Philippus Elsinga, W Vaalburg, and de Igle Jan Jong
Subjects: Biochemical recurrence, medicine.diagnostic_test, business.industry, Prostatectomy, Urology, medicine.medical_treatment, Brachytherapy, medicine.disease, Prostate cancer, medicine.anatomical_structure, Prostate, Positron emission tomography, Biopsy, Medicine, External beam radiotherapy, business, Nuclear medicine
Abstract: Rationale: The evaluation of the efficacy of the treatment of men with prostate cancer is largely based on post treatment levels of PSA. An increase in PSA or biochemical recurrence is the first sign of recurrent disease and precedes a clinically detectable recurrence by months to years. Digital rectal examination and conventional imaging techniques are not sensitive to detect a local recurrence. A metabolic imaging technique, which is not dependent on anatomical distortions, could be of use. In this study we investigated 11 C -choline positron emission tomography (PET) for the evaluation after treatment of localized prostate cancer. Methods: Thirty-six patients with localized prostate cancer, treated by either radical prostatectomy (n=20) or by external beam radiotherapy (n=16) were studied with 11 C -choline PET. The results of PET were compared with the results of histology and with clinical follow up. Results: Fourteen patients had no biochemical failure after therapy. 11 C -choline PET was true negative in 14/14 patients. Twenty-two patients had a biochemical failure. In the radical prostatectomy patients 11 C -choline PET was true positive in 5/13 (38%) cases. In the external beam radiotherapy patients 11 C -choline PET was true positive in 7/9 (78%). The recurrent tumor was confirmed by biopsy or by bone scan in eleven of the twelve true positive patients. In ten patients with a negative 11 C -choline PET scan, no recurrent tumor could be proven yet clinically, by biopsy or during follow up. Conclusion: 11 C -choline PET is a feasible technique for evaluation of treatment for localized prostate cancer. The site of recurrence was detected correctly in 78% of the patients after external beam radiotherapy compared to 38% of the patients after radical prostatectomy. No positive PET scans were observed sofar in patients with a serum PSA 11 C -choline PET compared to other imaging techniques.
Published: 2003
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8. Synthesis and evaluation of [18F]fluoroethyl SA4503 as a PET ligand for the sigma receptor

Author: W Vaalburg, Kazunori Kawamura, Philippus Elsinga, Tadayuki Kobayashi, Hideo Tsukada, Michio Senda, and K. Ishiwata
Subjects: Male, Fluorine Radioisotopes, medicine.medical_specialty, Central nervous system, Sigma receptor, Ligands, Binding, Competitive, Piperazines, Mice, Cellular and Molecular Neuroscience, In vivo, Internal medicine, medicine, Radioligand, Animals, Receptors, sigma, Rats, Wistar, Receptor, Nootropic Agents, Fluoroethyl, Neurons, Chemistry, Brain, Lipid Metabolism, Macaca mulatta, Rats, Viscera, Endocrinology, Pentazocine, medicine.anatomical_structure, Autoradiography, Dopamine Antagonists, Haloperidol, Ex vivo, Tomography, Emission-Computed, medicine.drug
Abstract: The sigma receptor might be involved in several diseases in the central nervous system. It occurs in the endocrine, immune, and other peripheral organ systems and is expressed in a variety of human tumors. The [18F]fluoroethyl analog of the sigma1-selective ligand SA4503 ([18F]FE-SA4503) was prepared and evaluated in animals to investigate its suitability for in vivo measurement of sigma receptors with positron emission tomography (PET). [18F]FE-SA4503 was synthesized by [18F]fluoroethylation of the corresponding O-demethyl precursor in an overall radiochemical yield of 4-7% (EOB) with a specific activity of >100 TBq/mmol. The radioligand had higher in vitro affinity for the sigma receptor than SA4503 (IC(50) sigma1 6.48 nM, IC50 sigma2 2.11 nM). [18F]FE-SA4503 was injected into mice. Uptake could be blocked by co-injection of the sigma receptor ligands haloperidol, pentazocine, and cold SA4503, but not with other receptor ligands. Ex vivo autoradiography studies in rats showed regional distribution in the brain similar to [11C]SA4503. Hippocampus, thalamus, and cortical areas were clearly delineated by [18F]FE-SA4503. The uptake was blocked by SA4503 treatment. In the rat brain, only a small portion of metabolites (6.6% of brain radioactivity) was detected at 30 min postinjection, whereas in plasma the fraction of metabolites amounted to 51.3% of plasma radioactivity. The kinetics of [18F]FE-SA4503 was measured with PET in the conscious monkey brain. High uptake values were found in the cortex, thalamus, cerebellum, and striatum, reaching a plateau value at 30 min postinjection. It is concluded that [18F]FE-SA4503 showed specific binding to sigma receptors in three animal species.
Published: 2002
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9. Quantifying drug-related 5-HT1A receptor occupancy with [F-18]MPPF

Author: W Vaalburg, RM Pieterman, Jan Passchier, A. van Waarde, Atm Willemsen, Groningen University Institute for Drug Exploration (GUIDE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: Agonist, medicine.medical_specialty, PINDOLOL, medicine.drug_class, POSTMORTEM, Pharmacology, Partial agonist, Buspirone, chemistry.chemical_compound, POSITRON-EMISSION-TOMOGRAPHY, Internal medicine, BINDING, SCHIZOPHRENIA, medicine, Radioligand, Pindolol, buspirone, occupancy, Chemistry, Binding potential, MAJOR DEPRESSION, HUMAN BRAIN, serotonin, ANTIDEPRESSANT DRUGS, Endocrinology, PET, [F-18]MPPF, SEROTONERGIC SYSTEM, 5-HT1A receptor, MPPF, medicine.drug
Abstract: Rationale: There is an increased interest in measuring the interaction of new or established drugs with their targets, in order to gain a better understanding of their mechanisms of action. PET can provide this information if an appropriate radioligand is available. [F-18]MPPF (4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[F-18]fluorobenzamido]ethylpiperazine) is a selective radioligand for serotonin 5-HT1A receptors. We have established that the binding potential (BP=B-max/K-D) of [F-18]MPPF for cerebral 5-HT1A receptors can be assessed in human brain without arterial sampling. Objectives: The aim of this study was to assess if 5-HT1A receptor occupancy can be measured through calculation of a drug-related decrease in BP with [F-18]MPPF and PET. Methods: Six volunteers were scanned twice using a Siemens Exact HR+ camera following injection of 70+/-18 MBq [F-18]MPPF (baseline and medicated conditions). Before the second scan, volunteers orally received either 3x10 mg pindolol at T=-15.5 h, T=-6.5 h, and T=-1.5 h (n=3) or 10 mg buspirone in a single dose at T=-1.5 h (n=3). Binding potentials were calculated using the simplified reference tissue model with the cerebellum as reference. Results: Administration of 30 mg pindolol led to a significant reduction in [F-18]MPPF binding potential of 42+/-17%. In contrast, no significant reduction of [F-18]MPPF binding potential was observed following administration of buspirone (5+/-17%). Conclusions: These results show that [F-18]MPPF can be used for measurement of drug-related 5-HT1A receptor occupancy and may be of particular interest in determining the 5-HT1A receptor interaction of new or established drugs in phase 1 and early phase 2 drug trials. Apparently, the 5-HT1A partial agonist buspirone is already clinically effective at low levels of 5-HT1A receptor occupancy.
Published: 2001
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10. Evaluation of Dissemination Studies with FDG Whole-Body Positron Emission Tomography in Patients with Suspected Metastatic Tumours of Brain and Spine

Author: H Haaxma-Reiche, Jan Pruim, TH Que, KG Go, W Vaalburg, Faculteit Medische Wetenschappen/UMCG, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: Adult, Male, medicine.medical_specialty, Pathology, Population, Autopsy, Metastasis, Fluorodeoxyglucose F18, Humans, Medicine, brain metastasis, education, Aged, Neuroradiology, dissemination study, education.field_of_study, Spinal Neoplasms, medicine.diagnostic_test, Brain Neoplasms, business.industry, Interventional radiology, Middle Aged, medicine.disease, CANCER, Positron emission tomography, [18F]-FDG whole body PET, Female, Surgery, Neurology (clinical), Neurosurgery, Radiology, Radiopharmaceuticals, business, Tomography, Emission-Computed, Brain metastasis
Abstract: Background. In the preoperative diagnosis of malignant brain tumours there is often uncertainty regarding their metastatic or primary nature, requiring dissemination studies. Currently FDG-wbPET is being used for the efficient detection of systemic tumours. It therefore may become a substitute for the conventional dissemination studies if it allows an earlier diagnosis. Method. In this descriptive and preliminary study a population of 14 patients with suspected or proven metastatic lesions, [18F]-fluoro-2-deoxy-D-glucose whole body positron emission tomography (FDG-wbPET) was conducted and verified by additional conventional dissemination studies. Findings and their Interpretation. The entire series of dissemination studies required an average of 30 days with a range of 4-73 days. The FDG-wbPET was corroborated by the other dissemination studies in 10 of the 14 patients. In 7 of these 10 patients both PET and dissemination studies showed systemic abnormal findings, but in one case the presence of high pulmonary activity on the FDG-wbPET and the abnormal findings on the chest X-rays proved to be Aspergillus infection at autopsy. In the other 2 cases the negative PET findings corresponded to the absence of systemic dissemination. In 5 cases there was disagreement of the results of the FDG-wbPET with other evidence, among which there were 2 cases of glioblastoma in which systemic metastases were most unlikely, and the foci of activity on the FDG-wbPET had to be considered as false positives. In the remaining 3 cases the systemic presence of high activity on the FDG-wbPET indicated the systemic presence of tumour, whereas the other dissemination studies disclosed no tumour. Conclusion. The results warrant the use of FDG-wbPET as a screening method for the search of metastases, allowing other studies to be focussed on the lesion. But from the cost/benefit point of view this would make the method less suitable as a substitute for dissemination studies in general, although it may speed up the diagnostic process.
Published: 2000
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11. Synthesis and biodistribution of [11C]procaterol, a β2-adrenoceptor agonist for positron emission tomography

Author: Philippus Elsinga, Ton J. Visser, P Doze, EA van der Wouden, W Vaalburg, van Aren Waarde, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: Male, Agonist, Biodistribution, medicine.medical_specialty, positron emission tomography, ADRENERGIC-RECEPTOR, Metabolic Clearance Rate, Hydrochloride, Procaterol, medicine.drug_class, Adrenergic beta-Antagonists, Propranolol, lung, Radioligand Assay, chemistry.chemical_compound, beta(2)-adrenoceptor, Isoprenaline, Internal medicine, medicine, Radioligand, Animals, PROCATEROL, Tissue Distribution, Carbon Radioisotopes, Rats, Wistar, DEPOSITION, agonist, SOLEUS MUSCLE, FORMOTEROL, Radiation, Antagonist, BETA-ADRENOCEPTOR STIMULANT, Adrenergic beta-Agonists, CARDIOVASCULAR-SYSTEM, Rats, Endocrinology, chemistry, [C-11]procaterol, VISUALIZATION, Receptors, Adrenergic, beta-2, RADIOTRACER, OPC-2009, Tomography, Emission-Computed, medicine.drug
Abstract: The potent, subtype-selective radioligand (+/-)-erythro-5-(1-hydroxy-2-[C-11]isopropyl-aminobutyl)-8-hydroxy-carbostyril ([C-11]procaterol) was synthesized and evaluated for visualization of pulmonary beta(2)-adrenoceptors with positron emission tomography (PET). Procaterol was labelled by reductive alkylation of the desisopropyl precursor with [C-11]acetone under the influence of NaCNBH3 and acetic acid. Synthesis and HPLC purification were performed in 34 min. Specific activities ranged from 26.5-39.3 TBq (about 700-1000 Ci)/mmol and the radiochemical yield was 2.4-8.6% (corrected for decay).Biodistribution studies were performed in male Wistar rats which were either untreated or predosed with (D,L)-propranolol hydrochloride (beta-adrenoceptor antagonist, 2.5 mg/kg), ICI 118551 (beta(2)-adrenoceptor antagonist, 0.15 mg/ kg), CGP 20712A (beta(1)-adrenoceptor antagonist, 0.15; mg/kg) or isoprenaline (B-adrenoceptor agonist, 15 mg/kg). Specific binding was observed in lungs, spleen and red blood cells, tissues known to contain beta(2)-adrenoceptors. Pulmonary binding was blocked by propranolol, ICI 118551 and isoprenaline, but not by CGP 20712A. This binding pattern is consistent with the beta(2) selectivity of the adioligand.The clearance of [C-11]procaterol was biphasic, with a rapid distribution phase (t(1/2) 0.17 min) representing 90% of the injected dose followed by an elimination phase (t(1/2) 18.1 min). About 45% of the plasma radioactivity was unmetabolized procaterol at 15 min postinjection.In a dynamic PET-study, the lungs of untreated control rats could barely be detected and total/non-specific binding ratios rose to only 1.2 at 20 min postinjection. Although labelling and administration of (-) erythro-procaterol the most active of 4 stereoisomers, may produce better results, [C-11]procaterol seems unsuitable for beta-adrenoceptor imaging. (C) 2000 Elsevier Science Ltd. All rights reserved.
Published: 2000
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12. Enhanced cerebral uptake of receptor ligands by modulation of P-glycoprotein function in the blood-brain barrier

Author: Philippus Elsinga, P Doze, NH Hendrikse, W Vaalburg, van Aren Waarde, Clinical pharmacology and pharmacy, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: BETA-ADRENERGIC-RECEPTOR, Adrenergic receptor, beta-adrenoceptors, Pharmacology, P-glycoprotein, Blood–brain barrier, RAT-BRAIN, Cellular and Molecular Neuroscience, Cyclosporin a, BINDING, medicine, ABSORPTION, Distribution (pharmacology), DRUGS, MULTIDRUG-RESISTANCE, Receptor, biology, Chemistry, blood-brain barrier, GENE, TRANSPORT, medicine.anatomical_structure, PET, LIPOPHILICITY, Knockout mouse, biology.protein, SECRETION, Efflux
Abstract: Low cerebral uptake of some therapeutic drugs can be enhanced by modulation of P-glycoprotein (P-gp), an ATP-driven drug efflux pump at the blood-brain barrier (BBB). We investigated the possibility of increasing cerebral uptake of the β-adrenergic ligands S-1'-[18F]-fluorocarazolol (FCAR) and [11C]-carazolol (CAR) in P-gp knockout mice (mdr1a (-/-)) and by modulation of P-gp with cyclosporin A (CsA) in rats. Specific and nonspecific binding of FCAR in the rat brain were doubled by CsA, while target/nontarget ratios and clearance from plasma (area under curve (AUG)) were not affected. Cerebral uptake of CAR in rats was much lower than FCAR and nonspecific. CsA increased this uptake 5-6-fold, not only due to P-gp modulation in the BBB but also to a 2-fold higher plasma AUG. In the CNS of mdr1a (-/-) mice, uptake of FCAR and CAR was, respectively, 2-fold and 3-fold higher than in mdr1a (+/+) mice. These results indicate that the cerebral uptake of β- adrenoceptor ligands can be increased by administration of P-gp modulators such as CsA without affecting regional distribution in the brain. P-gp modulation could improve the count statistics in PET studies of the CNS. (C) 2000 Wiley-Liss, Inc.
Published: 2000
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13. Mutagenic activity of a fluorinated analog of the beta-adrenoceptor ligand carazolol in the Ames test

Author: W Vaalburg, P Doze, Philippus Elsinga, A. van Waarde, E. F. J. de Vries, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: Salmonella typhimurium, GENETIC TOXICOLOGY, Cancer Research, Fluorine Radioisotopes, Magnetic Resonance Spectroscopy, Carazolol, Adrenergic beta-Antagonists, beta-adrenoceptors, In Vitro Techniques, Ligands, Weight Gain, PULMONARY, Mass Spectrometry, Ames test, Propanolamines, Mice, In vivo, BINDING, Animals, Radiology, Nuclear Medicine and imaging, CARCINOGENS, Rats, Wistar, Carcinogen, Chemistry, business.industry, Mutagenicity Tests, Antagonist, fluorine introduction, mutagenicity, Beta adrenoceptor, Ligand (biochemistry), Molecular biology, Acute toxicity, Rats, PET, Molecular Medicine, Radiopharmaceuticals, Nuclear medicine, business, Mutagens
Abstract: S-1'[F-18]-Fluorocarazolol (FCAR) is a fluorinated analog of the nonmutagenic beta-blocker carazolol (CAR). Tn former studies FCAR proved to be suitable for quantification of beta-adrenoceptors in vivo with positron emission tomography (PET). We report here that FCAR displays no acute toxicity in either rats or mice. However, FCAR induces a strong dose-related increase in the number of revertants in the Ames test. We conclude that FCAR yields mutagenic activity as measured by the Ames test. NUCL MED BIOL 27;3:315-319, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.
Published: 2000

14. Doppler broadening as a probe of the chemical environment following oxygen-14 decay

Author: S. Holm, Michael J. Schueller, W Vaalburg, Anne M. J. Paans, Mikael Jensen, and Robert J. Nickles
Subjects: Astrophysics::High Energy Astrophysical Phenomena, Resolution (electron density), Gamma ray, oxygen-14 decay, Nuclear isomer, Beta decay, Doppler broadening, chemistry.chemical_compound, Soda lime, chemistry, Gamma spectroscopy, Physics::Chemical Physics, Physical and Theoretical Chemistry, Atomic physics, Homogeneous broadening
Abstract: A search for the Doppler broadening following the beta decay of oxygen-14 was conducted with high resolution gamma spectroscopy on the 2313 keV gamma ray. Such a broadening should signal the mass of the labeled molecule and the nature of the stopping medium. Oxygen-14 labeled H2O, O2 and CO2 trapped on solid soda lime were investigated. No broadening was observed beyond the 1.65 keV instrumental resolution of the Ge detector, monitored by the unbroadened 2319 keV isomeric transition in 90Nb decay.
Published: 2000
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15. [Untitled]

Author: M. W. ter Steege, F Posthumus, P. K. Wiersema, [No Value] Stulen, and W. Vaalburg
Subjects: Spinacia, biology, food and beverages, Soil Science, Plant physiology, chemistry.chemical_element, Plant Science, biology.organism_classification, Nitrogen, chemistry.chemical_compound, chemistry, Nitrate, Environmental chemistry, Relative growth rate, Botany, Spinach, Ammonium, Chenopodiaceae
Abstract: Regulation of nitrate influx and efflux in spinach (Spinacia oleracea L., cv. Subito), was studied in short-term label experiments with 13N- and 15N-nitrate. Nitrate fluxes were examined in relation to the N demand for growth, defined as relative growth rate (RGR) times plant N concentration. Plants were grown at different nitrate concentrations (0.8 and 4 mM), with mineral composition of growth and uptake solutions identical.
Published: 1999
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16. Glucose consumption by various tissues in pregnant rats: effects of a 6‐day euglycaemic hyperinsulinaemic clamp

Author: A. M. J. Paans, Arie G. Nieuwenhuizen, Gerard A. Schuiling, Arend Bonen, T. R. Koiter, and W. Vaalburg
Subjects: Blood Glucose, Male, Fluorine Radioisotopes, positron emission tomography, muscle, WHITE ADIPOSE-TISSUE, Physiology, INVIVO, Muscle Proteins, Adipose tissue, TIME UPTAKE DATA, White adipose tissue, GRAPHICAL EVALUATION, Pregnancy, Brown adipose tissue, Hyperinsulinemia, Insulin, Tissue Distribution, INSULIN-RESISTANCE, Glucose Transporter Type 4, Glucose clamp technique, Adaptation, Physiological, adipose tissue, medicine.anatomical_structure, SKELETAL-MUSCLE, Female, MESSENGER-RNA, Tomography, Emission-Computed, medicine.medical_specialty, Monosaccharide Transport Proteins, brain, THERMOGENESIS, heart, Biology, liver, Insulin resistance, Internal medicine, medicine, Animals, Rats, Wistar, Muscle, Skeletal, Myocardium, medicine.disease, BRAIN TRANSFER CONSTANTS, TRANSPORT, Rats, Glucose, Endocrinology, Glucose Clamp Technique, biology.protein, Pregnancy, Animal, GLUT4, Thermogenesis
Abstract: In the course of pregnancy maternal tissues become increasingly more insensitive to insulin. As 6 days of euglycaemic hyperinsulinaemic clamping, from day 8 until 14 of gestation, ameliorates total glucose consumption, we analysed the contribution of individual tissues in this phenomenon. We measured not only glucose consumption, but also concentrations of the glucose transporter protein GLUT4 in selected tissues. On day 15 of pregnancy in saline-infused (pregnant control) rats. F-18-fluoro-2-deoxy-D-glucose (FDG) consumption, as measured by positron emission tomography, as well as GLUT4 content were diminished in heart (P
Published: 1998
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17. Growth requirement for N as a criterion to assess the effects of physical manipulation on nitrate uptake fluxes in spinach

Author: M. W. ter Steege, D. T. Clarkson, Ineke Stulen, Pieter J. C. Kuiper, P. K. Wiersema, W. Vaalburg, and A. J. M. Paans
Subjects: Spinacia, INFLUX, spinach, Physiology, chemistry.chemical_element, GUARD-CELLS, NO3 FLUXES, Plant Science, CORN ROOT-TISSUE, CALCIUM, chemistry.chemical_compound, BARLEY PLANTS, Nutrient, Animal science, Nitrate, nitrate, Spinacia oleracea, Relative growth rate, Botany, Genetics, Ammonium, Chenopodiaceae, net uptake rate, biology, Chemistry, Cell Biology, General Medicine, AMMONIUM, biology.organism_classification, Nitrogen, efflux, RGR, DEPENDENT ANION CHANNELS, NITROGEN, PLASMA-MEMBRANE, Spinach, N-15, N-13, physical handling
Abstract: The effects of physical manipulation of hydroponically grown plants of spinach (Spinacia oleracea L., cvs Subito and Glares) on nitrate uptake fluxes were studied in a long-term experiment (3 days), and in short-term label experiments (2 h) with N-13-nitrate and N-15-nitrate. In the long-term experiment, net nitrate uptake rate (NNUR) was measured by following the nitrate depletion in the uptake solution, which was replaced at regular intervals. In the short-term experiments, NNUR and nitrate influx were measured by simultaneous application of N-13-nitrate and N-15-nitrate. Plants were gently transferred into the labelled uptake solution, as is usually done in nutrient uptake studies. In addition, a more severe physical manipulation was carried out, including blotting of the roots, to mimic pretreatments which involve more handling of the plants prior to uptake measurements. Nitrate influx was measured immediately after physical manipulation and after 2 h of recovery. To assess the impact of the physical manipulation the experimentally determined nitrate uptake fluxes were compared with the N demand for growth, defined as relative growth rate (RGR) times plant nitrogen concentration (PNC) of parallel plants, which were left undisturbed.Nitrate influx and efflux were both subject to changes after physical manipulation of the plants. Physical handling, however, did not always result in an alteration of NNUR, which complicates the determination of the length of the recovery period. The impact of the handling and the time course of the recovery depended on the severity of the disturbance and were independent of the light conditions during the experiments. Even after a gentle transfer of the plants, recovery, in most cases, was not complete within 2 h. The data emphasise the need for minimal disturbance of plants during the last hours prior to nutrient uptake measurements.
Published: 1998

18. Synthesis and Evaluation of (S)-4-(3-(2‘-[11C]Isopropylamino)-2-hydroxypropoxy)-2H-benzimidazol-2-one ((S)-[11C]CGP 12388) and (S)-4-(3-((1‘-[18F]Fluoroisopropyl)amino)-2-hydroxypropoxy)-2H-benzimidazol-2-one ((S)-[18F]Fluoro-CGP 12388) for Visualization of β-Adrenoceptors with Positron Emission Tomography

Author: G Schreiber, A van Waarde, KA Jaeggi, M Heldoorn, Philippus Elsinga, and W Vaalburg
Subjects: Biodistribution, Stereochemistry, Chemistry, Carazolol, Drug Discovery, Radioligand, Molecular Medicine, Total synthesis, sense organs, Ligand (biochemistry), Fluoroacetone, Chemical synthesis, Isopropyl
Abstract: The beta-adrenoceptor antagonist (S)-[11C]CGP 12177 (4-(3-(tert-butylamino)-2-hydroxypropoxy)-2H-benzimidazol -2[11C]- one) is a generally accepted radioligand for cardiac and pulmonary PET studies. The synthesis of [11C]CGP 12177 is a laborious and often troublesome procedure. Therefore, (S)-CGP 12388 (4-(3-(isopropylamino)-2-hydroxypropoxy) -2H-benzimidazol-2-one), 5, the isopropyl analogue of CGP 12177, has been labeled with carbon-11 in the isopropyl group via a reductive alkylation by [11C]acetone (3) of the corresponding (S)-desisopropyl compound 2. The fluoro-substituted analogue of (S)-CGP 12388 was prepared by reacting 2 with [18F]fluoroacetone (4). (S)-[11C]CGP 12388 (5) was easily prepared via a one-pot procedure. The radiochemical yield of (S)-[11C]CGP 12388 (600-800 Ci/mmol, EOS) was 18% (EOB) with a total synthesis time of 35 min, whereas (S)-[18F]fluoro-CGP 12388 (6) (> 2000 Ci/mmol, EOS) was synthesized in 105 min with a radiochemical yield of 12% (EOB). Biodistribution studies in rats demonstrated specific binding to beta-adrenoceptors of (S)-[18F]fluoro-CGP 12388 and (S)-[11C]CGP 12388 in lung and heart. The lungs were clearly visualized with PET studies of rats. Total/nonspecific binding at 60 min postinjection was 5.6 for (S)-[11C]CGP 12388 and 2.0 for the (S)-18F compound. Due to its facile synthetic procedure and in vivo data, (S)-[11C]CGP 12388 is a promising beta-adrenoceptor ligand for clinical PET.
Published: 1997
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19. Coronary vasomotion in patients with syndrome X: evaluation with positron emission tomography and parametric myocardial perfusion imaging

Author: W Vaalburg, Jan Pruim, Kong I. Lie, Antonius Willemsen, Joan G. Meeder, EE vanderWall, Rutger L. Anthonio, Pk Blanksma, Rm Dejong, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: Adult, Male, perfusion heterogeneity, medicine.medical_specialty, positron emission tomography, ARTERY DISEASE, Coronary Disease, Angina, Coronary artery disease, Myocardial perfusion imaging, endothelial function, Internal medicine, INTRAVASCULAR ULTRASOUND, medicine, Humans, Radiology, Nuclear Medicine and imaging, Endothelial dysfunction, BLOOD-FLOW, medicine.diagnostic_test, business.industry, Cold pressor test, Heart, Dipyridamole, General Medicine, Middle Aged, syndrome, ANGINA-PECTORIS, medicine.disease, Coronary Vessels, Cold Temperature, Perfusion, Vasomotor System, MICROVASCULAR ANGINA, perfusion reserve, RESERVE, ATHEROSCLEROSIS, ENDOTHELIAL DYSFUNCTION, CHEST PAIN, Cardiology, Female, Normal Coronary Arteriogram, Endothelium, Vascular, N-13 AMMONIA, business, Tomography, Emission-Computed, medicine.drug
Abstract: The aim of this study was to elucidate further the causative mechanism of abnormal coronary vasomotion in patients with syndrome X. In patients with syndrome X, defined as angina pectoris and documented myocardial ischaemia during stress testing with normal findings at coronary angiography, abnormal coronary vasomotion of either the micro- or the macrocirculation has been suggested as the causative mechanism. Accordingly, we evaluated endothelial function, vasodilator reserve, and perfusion heterogeneity in these patients. Twenty-five patients with syndrome X (definitely normal coronary arteriogram, group A), 15 patients with minimal coronary artery disease (group B) and 21 healthy volunteers underwent [13N]ammonia positron emission tomography at rest, during cold pressor stimulation (endothelial function) and during dipyridamole stress testing (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by parametric polar mapping using a 480-segment model. In both patient groups, resting perfusion was increased compared to the normal subjects: group A, 127+/-31 ml.min-1.100 g-1; group B, 124+/-30 ml.min-1.100 g-1 normal subjects, 105+/-21 ml.min-1.100 g-1 (groups A and B vs normals, P0.05). These differences were abolished after correction for rate-pressure product. During cold pressor stimulation, the perfusion responses (ratio of cold pressor perfusion to resting perfusion) were similar among the patients and the control subjects (group A, 1.20+/-0.23; group B, 1.24+/-0.22; normal subjects, 1.23+/-0.14). Likewise, during dipyridamole stress testing, perfusion responses were similar among the three groups (group A, 2.71+/-0.67; group B, 2.77+/-1.29; normal subjects, 2. 91+/-1.04). In group A the heterogeneity of resting perfusion, expressed as coefficient of variation, was significantly different from the volunteers (20.1+/-4.5 vs 17.0+/-3.0, P0.05). In group B (coefficient of variation 19.4+/-3.9) the difference from normal volunteers was not significant. In this study, patients with syndrome X and patients with minimal coronary artery disease showed normal perfusion responses during cold pressor stimulation and dipyridamole stress testing. Our findings therefore suggest that endothelial dysfunction and impaired vasodilator reserve are of no major pathophysiological relevance in patients with syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal release of vasoactive substances may play a role in the pathogenesis of syndrome X.
Published: 1997
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20. Stereoselective Synthesis and Biodistribution of Potent [11C]-Labeled Antagonists for Positron Emission Tomography Imaging of Muscarinic Receptors in the Airways

Author: G. Visser, T W van der Mark, Ton J. Visser, K Ensing, T Jansen, W Vaalburg, Jan Kraan, van Aren Waarde, Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Faculty of Science and Engineering
Subjects: Male, Biodistribution, Tertiary amine, ENANTIOMERS, INVIVO, Respiratory System, SUBTYPES, 4-DAMP, chemistry.chemical_compound, In vivo, Drug Discovery, Muscarinic acetylcholine receptor, medicine, Radioligand, Animals, Tissue Distribution, Rats, Wistar, Methiodide, Receptor, Receptor, Muscarinic M3, Receptor, Muscarinic M2, ANALOGS, Receptor, Muscarinic M1, Muscarinic antagonist, Stereoisomerism, QUANTIFICATION, Receptors, Muscarinic, Molecular biology, Rats, Kinetics, chemistry, Biochemistry, CELLS, Molecular Medicine, BENZILATE, LUNG, BINDING-PROPERTIES, Tomography, Emission-Computed, medicine.drug
Abstract: Quantitation of muscarinic receptors in the lungs in vivo with positron emission tomography (PET) is of clinical interest. For that purpose we decided to develop [C-11]-labeled ligands with a high affinity (K-D
Published: 1997
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21. Effects of permanent dual chamber pacing on myocardial perfusion in symptomatic hypertrophic cardiomyopathy

Author: Hjgm Crijns, E. E. van der Wall, W Vaalburg, Pk Blanksma, J. L. Posma, and Kong I. Lie
Subjects: Adult, Male, medicine.medical_specialty, Heart disease, perfusion imaging, Hemodynamics, Perfusion scanning, METABOLISM, Angina Pectoris, Coronary circulation, Coronary Circulation, Internal medicine, medicine, Humans, Sinus rhythm, Aged, pacing, BLOOD-FLOW, ABNORMALITIES, business.industry, REST, Cardiac Pacing, Artificial, Hypertrophic cardiomyopathy, Cardiomyopathy, Hypertrophic, Middle Aged, hypertrophic cardiomyopathy, CORONARY FLOW, medicine.disease, ISCHEMIA, Perfusion, Dipyridamole, RESERVE, medicine.anatomical_structure, Anesthesia, Cardiology, Female, SCINTIGRAPHY, OBSTRUCTION, N-13 AMMONIA, Cardiology and Cardiovascular Medicine, business, Research Article, Tomography, Emission-Computed, medicine.drug
Abstract: OBJECTIVE: Angina and the presence of myocardial ischaemia are common in hypertrophic cardiomyopathy. Dual chamber pacing results in clinical improvement in these patients. This study evaluates the effects of permanent dual chamber pacing on absolute regional myocardial perfusion and perfusion reserve. SETTING: University hospital. PATIENTS AND DESIGN: Six patients with hypertrophic cardiomyopathy and severe symptoms of angina received a dual chamber pacemaker. Absolute myocardial regional perfusion and perfusion reserve (dipyridamole 0.56 mg/kg) were measured by dynamic positron emission tomography with 13N-ammonia both during sinus rhythm and 3 months after pacemaker insertion. Results were compared with those from 28 healthy volunteers. RESULTS: Pacing resulted in a reduction of anginal complaints and a reduction in intraventricular pressure gradient from 65 (SD 30) mm Hg to 19 (10) mm Hg. During sinus rhythm, baseline perfusion was higher in patients with hypertrophic cardiomyopathy than controls (184 (31) v 106 (26) ml/min/100 g, P < 0.01), and perfusion reserve was lower (1.6 (0.4) v 2.8 (1.0), P < 0.05). During pacing myocardial perfusion decreased to 130 (27) ml/min/100 g (P < 0.05), with variable responses in terms of perfusion reserve. Pacing caused a redistribution of myocardial stress perfusion and perfusion reserve. The coefficient of regional variation of myocardial stress perfusion decreased from 19.7 (7.0)% to 14.6 (3.9)% during pacing (12.9 (3.8)% in controls, P < 0.01). The coefficient of regional variation of perfusion reserve decreased from 16.7 (6.6)% to 11.4 (2.6)% during pacing (9.8 (4.1)% in controls, P < 0.01). CONCLUSIONS: Pacing caused a decrease of resting left ventricular myocardial blood flow and blood flow during pharmacologically induced coronary vasodilatation. Although global perfusion reserve remained unchanged, myocardial perfusion reserve became more homogeneously distributed.
Published: 1996
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22. Synthesis and organ distribution of [18F]fluoro-org 6141 in the rat: A potential glucocorticoid receptor ligand for positron emission tomography

Author: W Vaalburg, Gert Luurtsema, Er Dekloet, Béla Bohus, G. Visser, van Aren Waarde, Philippus Elsinga, HJ Krugers, Mb Groen, K. G. Go, Jakob Korf, and Anne M. J. Paans
Subjects: Male, Fluorine Radioisotopes, Cancer Research, medicine.medical_specialty, Biodistribution, Ligands, Radioligand Assay, Receptors, Glucocorticoid, Glucocorticoid receptor, Drug Stability, Pharmacokinetics, Internal medicine, medicine, Radioligand, Animals, Tissue Distribution, Radiology, Nuclear Medicine and imaging, Rats, Wistar, Dexamethasone, Chemistry, Rats, Endocrinology, Isotope Labeling, Molecular Medicine, Specific activity, Norprogesterones, Glucocorticoid, Ex vivo, Tomography, Emission-Computed, medicine.drug
Abstract: For the synthesis of [18F]Fluoro-Org 6141 via a nucleophilic substitution reaction with 18F-, the tosyl group was chosen as the leaving group because of its stability and excellent leaving group ability. The biodistribution of the high affinity and moderate lipophilicity (log P = 2.66, calculated value) ligand [18F]Fluoro-Org 6141 (specific activity 8.2 to 37 TBq/mmol, yield 10% at EOB) was examined in sham adrenalectomized (sADX) and adrenalectomized (ADX) male Wistar rats. Two days after ADX or sADX, the animals were anesthetized and 0.37 to 1.85 MBq of [18F]Fluoro-Org 6141 was administered intravenously. Kinetics of 18F activity uptake were monitored for 3 h using a stationary double-headed positron emission tomography (PET) camera, and the biodistribution was assessed by ex vivo determination of radioactivity in several tissues and different brain areas. One hour after injection of the radioligand, the bladder, kidney, liver, trachea, and bone of sADX animals contained more concentration on a wet weight basis than blood. Three hours post injection, radioactivity was retained in bladder, trachea, and bone. The accumulation of radioactivity in brain corresponded to the concentration of activity in the blood within the first hours after injection. ADX animals showed a higher uptake of 18F activity in spleen, testes, and brain areas (hippocampus and brainstem) but a lower uptake in bone than sADX rats. PET scans suggested that 18F activity uptake in the brain had not yet reached a maximum at this interval. Although [18F]Fluoro-Org 6141 is not useful for PET studies of glucocorticoid receptors (GRs), the results obtained with this compound indicate a synthetic strategy suitable for the synthesis of high-affinity radioligands for GRs.
Published: 1995
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23. Brain tumors

Author: W Vaalburg, Martinus Heesters, Eric J. F. Franssen, Antonius Willemsen, Anne M. J. Paans, A. van Waarde, KG Go, Jan Pruim, Gerben M. Visser, and W M Molenaar
Subjects: Adult, Male, Vasculitis, Pathology, medicine.medical_specialty, CARBON-11-METHIONINE, RADIONUCLIDE STUDIES, POSITRON EMISSION TOMOGRAPHY, Brain tumor, Infarction, METABOLISM, Metastasis, GLUCOSE, Meningioma, Methionine, BRAIN NEOPLASMS, RADIONUCLIDE STUDIES, LUMPED CONSTANT, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Carbon Radioisotopes, Neoplasm Metastasis, BRAIN NEOPLASMS, EMISSION CT (ECT), TREATMENT RESPONSE, Aged, medicine.diagnostic_test, EMISSION CT (ECT), FLUORINE-18-FLUORODEOXYGLUCOSE, business.industry, Lymphoma, Non-Hodgkin, BRAIN NEOPLASMS, Cancer, Glioma, Middle Aged, medicine.disease, GLIOMAS, CANCER, Lymphoma, Neoplasm Proteins, Positron emission tomography, Tyrosine, Female, business, Nuclear medicine, Tomography, Emission-Computed, DEOXYGLUCOSE
Abstract: PURPOSE: Positron emission tomography (PET) with the amino acid tracer L-[1-C-11]-tyrosine was evaluated in 27 patients with primary and recurrent brain tumors.MATERIALS AND METHODS: Patients underwent either static (n = 14) or dynamic PET (n = 13), with quantification of protein synthesis rate (PSR) and tumor-to-background ratio. Findings were compared with histologic findings.RESULTS: Primary brain tumor was proved in 22 patients histologically, as well as metastatic cancer of unknown origin, primary non-Hodgkin lymphoma, meningioma, atypical infarction, and vasculitis in one patient each. At PET, 20 of 22 primary tumors, the metastasis, and non-Hodgkin lymphoma were correctly depicted. A false-positive finding was obtained with the infarction, and the meningioma and vasculitis were not depicted. The calculated sensitivity was 92%; specificity, 67%; and accuracy, 89%. There were no statistically significant relationships between histologic findings, PSR, and tumor-to-background ratio.CONCLUSION: L-[1-C-11]-tyrosine is a valid tracer for diagnosis of brain tumors and allowed quantification of PSR.
Published: 1995
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24. Localised proton spectroscopy and spectroscopic imaging in cerebral gliomas, with comparison to positron emission tomography

Author: W Vaalburg, E. L. Mooyaart, K. G. Go, Jan Pruim, Anne M. J. Paans, R. L. Kamman, Martinus Heesters, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: Fluorine Radioisotopes, Pathology, Magnetic Resonance Spectroscopy, PH, POSITRON EMISSION TOMOGRAPHY, Metabolite, INVIVO, Brain Edema, chemistry.chemical_compound, Nuclear magnetic resonance, Medicine, Carbon Radioisotopes, Phosphocholine, medicine.diagnostic_test, Brain, Glioma, GLIOMAS, Magnetic Resonance Imaging, medicine.anatomical_structure, Positron emission tomography, NMR-SPECTROSCOPY, Lactates, Cardiology and Cardiovascular Medicine, Tomography, Emission-Computed, medicine.medical_specialty, Phosphorylcholine, METABOLISM, Deoxyglucose, Grey matter, RAT-BRAIN, Creatine, H-1 MR SPECTROSCOPY, HUMAN BRAIN-TUMORS, White matter, Fluorodeoxyglucose F18, PROTON MAGNETIC RESONANCE SPECTROSCOPY, (CO2)-C-11, Humans, Radiology, Nuclear Medicine and imaging, Lactic Acid, Brain Chemistry, Aspartic Acid, L-ASPARTIC ACID, business.industry, Supratentorial Neoplasms, Magnetic resonance imaging, medicine.disease, PROTON MAGNETIC RESONANCE SPECTROSCOPIC IMAGING, PET, chemistry, Tyrosine, Neurology (clinical), business
Abstract: In 32 patients with gliomas, one- and two-dimensional proton magnetic resonance spectroscopy (H-1-MRS) has been conducted, the latter allowing reconstruction of spectroscopic data into a spectroscopic image (MRSI), showing the distribution of the various metabolite concentrations over the cross-sectional plane. For lack of absolute concentrations, the measured concentrations of phosphocholine (CHOL), N-acetyl-L-aspartate (NAA), and lactate (LAG) were conventionally expressed in ratios relative to that of creatine (CREAT). Compared to normal brain tissue, an increased CHOL/CREAT ratio was found in all groups of tumours, in glioblastomas, high-, middle- and low-grade astrocytomas both at the margin and the core of the tumours, but in oligodendrogliomas only at the margin. This is consistent with an increased phosphocholine turnover in relation to membrane biosynthesis by the proliferating cells. The NAA/CREAT ratio was decreased in all groups of tumours, both in the centre and at the margin, reflecting replacement of functioning neurons by neoplastic cells. The LAG/CREAT ratio was elevated in the core of malignant gliomas, which may be the result of a prevailing glycolysis, characteristic of tumours, possibly in conjunction with hypoxia/ischaemia. In the perifocal oedema, there was neither elevation of the CHOL/CREAT ratio nor decrease of the NAA/CREAT ratio; an increased LAC/CREAT ratio therefore rather reflected ischaemia/hypoxia probably due to locally elevated pressure and compromised regional perfusion. In the normal brain, the metabolite ratios of grey matter did not differ from those of white matter. The frontal lobe and basal ganglia showed lower NAA/CREAT ratios than the other cerebral areas. In 7 patients positron emission tomography was also performed with [F-18] fluoro-2-deoxy-D-glucose ((18)FDG) or L-[1-C-11]-tyrosine (C-11-TYR); the latter demonstrated a pattern of C-11-TYR uptake similar to that of CHOL elevation in the MRSI.
Published: 1995
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25. QUANTIFICATION OF AN C-11 LABELED BETA-ADRENOCEPTOR LIGAND, S-(-)CGP-12177, IN PLASMA OF HUMANS AND RATS

Author: Pk Blanksma, A vanWaarde, Ama Weemaes, H Posthumus, Ton J. Visser, Ph Elsinga, Amj Paans, W Vaalburg, Rl Anthonio, Gerben M. Visser, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: Adult, Male, Metabolite, POSITRON EMISSION TOMOGRAPHY, Adrenergic beta-Antagonists, Ligands, High-performance liquid chromatography, METABOLITES, Propanolamines, CGP-12177, chemistry.chemical_compound, ANTAGONISTS, CGP 12177, Blood plasma, BINDING, SUITABILITY, Radioligand, Animals, Humans, Rats, Wistar, Trichloroacetic acid, ASYMMETRIC-SYNTHESIS, Biotransformation, Chromatography, High Pressure Liquid, IN-VIVO, Carbon Isotopes, Chromatography, Chemistry, Blood Proteins, General Chemistry, Metabolism, Ligand (biochemistry), Rats, PET, Injections, Intravenous, Female, Chromatography, Thin Layer, Quantitative analysis (chemistry), Half-Life, Protein Binding
Abstract: β-Adrenoceptors in human lungs and heart can be imaged with the radioligand 4-[3-[(1,1-dimethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-11C-one (CGP 12177, [11C]I). For quantification of receptor density with compartment models by adjustment of rate constants, an ‘input function’ is required which consists of the integral of the concentration of unmodified ligand in arterial plasma over time. A discrepancy in the literature regarding metabolic stability of [11C]I prompted us to study metabolism in rats by reversed-phase HPLC (RP-HPLC) of trichloroacetic acid extracts of arterial plasma after i.v. injection of [11C]I (> 11.1 TBq/mmol, 11 MBq/kg). Some plasma samples were also directly applied to an internal-surface reversed-phase (ISRP) column. In parallel experiments, tritiated [11C]I was employed and methanol extracts of arterial plasma were analyzed by straight-phase TLC. The three methods were in excellent agreement. Unmodified [11C]I decreased from > 98.5% ( 3 H ) or > 99.9% ( 11 C ) initially to 57 ± 7% at 80 min post injection to formation of two polar metabolites. Using the RP-HPLC method, no metabolism was detectable in humans up to 30 min after injection of [11C]I (1851 MBq). Deproteinization of plasma with acetonitrile resulted in the formation of a radioactive species (artifact) which eluted immediately after the void volume in RP-HPLC and which could be mistakenly interpreted as a metabolite. Plasma protein binding was low (ca. 30%) in both humans and rats. Association of the radioligand to blood cells suggested that equilibrium between receptor-bound and free radioligand was reached within 15 min after high-specific-activity injections, but only after more than 30 min after low-specific-activity injections.
Published: 1995
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26. Abstracts of papers and posters

Author: R. L. Anthonio, A. T. M. Willemsen, T. Visser, A. Waarde, P. Elzinga, A. Weemaes, J. G. Meeder, J. Pruim, G. Visser, P. K. Blanksma, W. Vaalburg, P. G. M. Bloemen, P. A. J. Henricks, L. Bloois, M. C. Tweel, F. P. Nijkamp, D. J. A. Crommelin, G. Storm, A. H. Boer, H. M. I. Winter, C. F. Lerk, J. Boer, H. Meurs, A. E. Bottone, M. Koopal, J. C. Visser, J. Zaagsma, P. Borger, H. F. Kauffman, J. L. J. Vijgen, D. S. Postma, E. Vellenga, Theresa L. Buckley, H. Buikema, W. H. Gilst, D. J. Veldhuisen, B. J. G. L. Smet, E. Scholtens, K. I. Lie, H. Wesseling, P. K. Cheung, F. W. D. Dijkhuis, W. W. Bakker, J. Visser, R. P. Coopes, L. Benthem, J. Leest, A. F. Roffel, R. P. Coppes, L. J. W. Zeilstra, A. Vissink, A. W. T. Konings, M. Dijkstra, G. In't Veld, M. Müller, G. J. Berg, F. Kuipers, R. J. Vonk, P. H. Elsinga, E. J. F. Franssen, W. T. A. Graaf, E. G. E. Vries, G. M. Visser, M. G. Vos, A. H. Braker, T. J. Visser, F. Engels, A. H. Houwelingen, M. J. Velde, R. T. Gansevoort, W. J. Sluiter, M. H. Hemmelder, D. Zeeuw, P. E. Jong, H. P. M. M. Gelissen, R. H. Henning, A. H. Epema, J. Eekeren, P. J. Hennis, A. Hertog, S. S. N. Graaf, S. J. Kellie, H. Bloemhof, I. Johnston, M. Besser, R. W. Chaseling, R. A. Ouvrier, D. R. A. Uqes, A. Haan, H. J. Geerligs, J. P. Huchshorn, G. J. M. Scharenburg, J. Wilschut, M. Haas, C. A. Kluppel, D. K. F. Meijer, F. Moolenaar, Eibert R. Heerdink, Hubert G. Leufkens, Ron M. C. Herings, Bruno H. Ch. Stricker, Albert Bakker, W. F. Heesen, F. W. Beltman, A. J. Smit, J. F. May, B. Meyboom-de Jong, M. Duin, J. Akker, M. F. W. Pas, J. P. Popta, S. A. Nelemans, H. J. Linde, A. Boer, F. Sturmans, E. M. Hessel, A. J. M. Oosterhout, C. L. Hofstra, J. Garssen, H. Loveren, H. F. J. Savelkoul, Y. Hoekstra, E. J. M. Weersink, J. W. Jong, B. Belt-Gritter, Lisa M. Jonkman, Chantal Kemner, Harry S. Koelega, Herman Engeland, Marinus N. Verbaten, M. Kalivianakis, I. Zijlstra, H. J. Verkade, H. Elzinga, F. Stellaard, J. A. A. M. Kamps, P. J. Swart, H. Morselt, G. L. Scherphof, J. L. Kenemans, M. M. Lorist, N. R. Koopen, A. D. Kraneveld, A. Si. Koster, M. E. Kuipers, M. Groenink, H. Huisman, H. Schuitemaker, H. S. Lau, I. J. P. M. Broek, A. Dijk, J. Oostinga, A. J. Porsius, Y. Lin, R. Havinga, R. J. Meijer, Th. W. Mark, G. H. Koëter, A. A. Michels, V. -T. Nguyen, O. Bensaude, H. H. Kampinga, Inge C. M. Mohede, J. M. Antoon, Grietje Molema, Thomas S. Edgington, Philip E. Thorpe, P. Olinga, G. W. Sandker, M. J. H. Slooff, M. T. Merema, G. M. M. Groothuis, G. Hofman, I. Ark, J. J. C. Paulussen, M. J. E. Fischer, N. J. Mol, L. H. M. Janssen, E. Th. J. Peters, G. Th. Werf, F. M. Haaijer-Ruskamp, Yigal M. Pinto, Gerrit Rooks, Jean G. Grandjean, Tjark Ebels, H. Schunkert, Frank A. Redegeld, Johan Garssen, Henk Loveren, Irma M. Rigter, Muck Groningen, Gertjan J. Boks, Jan P. Tollenaere, Keith I. Trollope, Jeremy G. Vinter, Gudarz Sadeghi Hashjin, Gert Folkerts, Peet G. F. Loo, R. E. Santing, C. G. Olymulder, K. Molen, Y. Pasman, Heleen Scheerens, T. J. A. Seppenwoolde-Waasdorp, P. Boer, H. M. J. Engelen, J. H. H. Thijssen, R. A. A. Maes, J. Smit, J. W. Smit, H. Steen, M. H. Steurs, P. F. M. Kuks, J. A. Leusink, Balázs M. Szabó, Harry J. G. M. Crijns, Ans C. P. Wiesfeld, H. Talsma, J. C. H. Borchert, M. J. Steenbergen, W. E. Hennink, K. B. Teeuw, H. Cromheecke, A. Schreudering, B. C. H. Teisman, W. Maselbas, G. T. P. Wolters-Keulemans, R. G. Tieleman, C. D. J. Langen, K. Bel, H. J. G. M. Crijns, J. Grandjean, M. Wijffels, A. H. Klimp, P. F. Meer, M. A. Allessie, H. A. Tissot Patot, B. M. Jongh, Y. S. Tuininga, J. Brouwer, J. Haaksma, A. J. Man in't Veld, F. J. Blomjous, M. H. Vingerhoeds, S. O. Belliot, H. J. Haisma, C. A. Visscher, R. M. Huisman, G. J. Navis, J. F. Vlieger, P. Wijngaard, J. Wilting, D. Heuven-Nolsen, A. A. Voors, B. L. Brussel, H. W. M. Plokker, R. C. A. M. Waardenburg, Prins J. Meijer, C. Vries, N. H. Mulder, P. K. Wierenga, P. Schoen, and R. Bron
Subjects: Pharmacology, Pharmaceutical Science, Pharmacology (medical), Pharmacy, General Medicine, Toxicology
Published: 1994
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27. Metabolism of a [18F]fluorine labeled progestin (21 -[18F]fluoro-16α -ethyl-19-norprogesterone) in humans: a clue for future investigations

Author: Gert Luurtsema, K.G. Go, M. Studeny, W Vaalburg, G. Visser, O.E. Nieweg, E. van der Ploeg, A. Verhagen, Mels Sluyser, and C.C.J. De Goeij
Subjects: Fluorine Radioisotopes, Cancer Research, medicine.medical_specialty, medicine.drug_class, Metabolite, Estrogen receptor, Breast Neoplasms, In Vitro Techniques, Biology, Gas Chromatography-Mass Spectrometry, Mice, chemistry.chemical_compound, In vivo, Internal medicine, medicine, Animals, Humans, Radiology, Nuclear Medicine and imaging, Receptor, Biotransformation, Screening procedures, Brain Neoplasms, Mammary Neoplasms, Experimental, Cancer, medicine.disease, Imaging agent, Endocrinology, Receptors, Estrogen, chemistry, Estrogen, Cancer research, Molecular Medicine, Meningioma, Receptors, Progesterone, Norprogesterones, Tomography, Emission-Computed
Abstract: Assessment of estrogen receptors and progesterone receptors (PR) with PET may allow the determination of the hormone responsiveness of tumors without the need for multiple biopsies, and the monitoring of the effect of hormonal therapy. In spite of the favourable characteristics of 21-[ 18 F]fluoro-16α-ethyl-19-norprogesterone ([ 18 F]FENP) found in preclinical studies, the compound failed to reveal the presence of PR in breast carcinomas and meningiomas. In view of the clinical significance of the PR assay in human breast cancer, it is worthwhile to explore mechanisms that are potentially involved in the inadequacy of [ 18 F]FENP to image PR with PET. Our present study on the in vivo metabolism of [ 18 F]FENP in humans demonstrates a rapid clearance and biotransformation of the compound. Results of incubation experiments suggest that the metabolic conversion of [ 18 F]FENP is not restricted to the liver, but also occurs in blood cells (presumably the erythrocytes) and tumors (breast carcinomas and meningiomas). The predominant metabolite of [ 18 F]FENP in plasma during the rapid distribution phase and in tumors is identified as 20-dihydro-[ 18 F]FENP. The conversion of [ 18 F]FENP to its 20α- or 20β-hydroxy metabolite has a deleterious effect on the binding affinity for PR. Our findings do not justify a conclusion as to the extent of in vivo extrahepatic biotransformation of [ 18 F]FENP, or its significance in the ineffectiveness of [ 18 F]FENP as an imaging agent for PR. On the other hand, the ability of breast carcinomas and meningiomas to metabolize [ 18 F]FENP avidly appears to preclude selective imaging of PR in these tumors during the time of a PET examination. It is imperative to evaluate the metabolic stability of a [ 18 F]fluorine labeled progestin in an early stage of future screening procedures.
Published: 1994
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28. Fourth meeting of the European Neurological Society 25–29 June 1994 Barcelona, Spain

Author: H. Hattig, C. Delli Pizzi, M. C. Addonizio, Michelle Davis, A. R. Giovagnoli, L. Florensa, M. Roth, J. de Kruijk, Francisco Lacruz, Ph. Dewailly, A. Toygar, C. Avendano, P.P. De Deyn, J. F. Hurtevent, F. Lomeila, T. W. Wong, Gordon T. Plant, M. Bud, H. J. Willison, DH Miller, D. W. Langdon, R. Cioni, J. Servan, A. Kaygisiz, E. Racadot, D. B. Schens, E. Picciola, L. Falip, C. Bouchard, J. Jotova, A. Jorge-Santamaria, P. Misra, A. Dufour, C. P. Panagopoulos, A. Venneri, B. Sredni, B. Angelard, M. Janelidze, M. Carreno, J. Obenberger, J. Pouget, H. W. Moser, R. Kaufmann, J. A. Molina, D. Linden, A. Martin Urda, E. Uvestad, A. Krone, J. P. Cochin, J. Mallecourt, A. Cambon-Thomsen, K. Violleau, P. Osschmann, A. M. Durocher, E. Bussaglia, D. M. Danielle, H. Efendi, C. Van Broeckhoven, K. G. Jordan, W. Rautenberg, C. Iniguez, J. M. Delgado, Graham Watson, M. Lawden, Gareth J. Barker, K. Stiasny, James T. Becker, G. Campanella, E. Peghi, A. Poli, A. Haddad, T. Yamawaki, Giacomo P. Comi, S. Sotgiu, B. Ersmark, A. Pomes, M. Ziegler, P. Ferrante, P. Ruppi, H. KuÇukoglu, R. Bouton, U. K. Rinne, P. Vieregge, M. Dary, P. Giunti, Peter J. Goadsby, S. Jung, E. Secor, A. Steinberg, N. Vila, M. A. Hernandez, M. Cursi, A. Enqelhardt, A. Engelhardt, J. Veitch, F. Di Silverio, F. Arnaud, B. Neundörfer, R. Brucher, Dominique Caparros-Lefebvre, B. Meyer, Marianne Dieterich, M. H. Snidaro, R. Gomez, R. Cerbo, M. Ragno, J. M. Vance, S. Nemni, A. Caliskan, F. Barros, I. Velcheva, D. Ceballos-Baumann, V. Barak, A. Avila, N. Antonova, F. Resche, S. Pappata, L. Varela, S. R. Silveira Santos, A. Cammarota, L. Naccache, Y. Nara, E. Tournier-Lasserves, R. Mobner, T. Chase, A. Ensenyat, J. Ulrich, G. Giegerich, M. Rother, M. Revilla, N. Nitschke, K. Honczarenko, E. Basart Tarrats, J. Blin, B. Jacob, J. Santamaria, S. Knezevic, J. L. Castillo, M. Antem, J. Colomer, O. Busse, Didier Hannequin, S. Carrier, J. B. Ruidavets, C. Rozman, J. Bogoussslavsky, J. Pascual Calvet, E. Monros, J. M. Polo, M. Zucconl, Javier Muruzabal, R. R. Allen, R. Rivolta, K. Haugaard, A. Nespolo, K. Hoang-Xuang, G. Bussone, T. Avramidis, E. Corsini, Christiana Franke, T. Vinogradova, H. Boot, K. Vestergaard, G. H. Jansen, N. Argentino, M. Raltzig, W. Linssen, Mark B. Pepys, P. Roblot, L. Lauritzen, E. Fainardi, D. Morin, T. X. Arbizu Urdiain, J. Wollenhaupt, S. Bostantjopoulou, G. Pavesi, A. D. Forman, Giovanni Fabbrini, D. Jean, J. J. Archelos, M. I. Blanchs, M. Del Gobbo, Anna Carla Turconi, Ch. Derouesné, Elio Scarpini, A. Visbeck, P. Castejon, J. P. Renou, F. Mounier-Vehier, G. Potagas, Ch. Duyckaerts, A. Filla, R. Schneider, G. Ronen, K. Nagata, J. P. Vedel, A. Henneberg, G. van Melle, C. Baratti, H. Knott, M. C. Prevett, A. Bes, B. Metin, Jos V. Reempts, L. Martorell, Mefkure Eraksoy, H. O. Handwerker, D. S. Younger, O. Oktem, D. Frongillo, C. Soriano-Soriano, L. Niehaus, F. Zipp, A. Tartaro, S Newman, R. H. Browne, P. Davous, R. Sanchez, M. Muros, M. E. Kornhuber, A. Lavarone, M. Mohr, M. R. Garcia, S. Russell, H. Kellar-Wood, M. R. Tola, B. Ostermeyer, Ch. Tzekov, K. Sartor, E. B. Ringelstein, P. P. Gazzaniga, Paul Krack, H. Fidaner, H. Rico, T. Dbaiss, F. Alameda, E. Torchiana, L. Rumbach, I. Charques, J. M. Bogaard, C. D. Frith, L. J. Rappelle, R. Brenner, A. Joutel, K. Fuxe, G. HÄcker, M. J. Blaser, J. Valls-SolÇ, G. Ulm, M. Alberdi, A. Bock, F. W. Bertelsmann, U. Wieshmann, J. Visa, J. R. Lupski, D. D'Amico, L. M. P. Ramos, A. A. Vanderbark, R. Horn, M. Warmuth, Dietmar Kühne, Mark S. Palmer, C. Ehrenheim, E. Canga, S. Viola, O. Scarpino, P. Naldi, R. Almeida, A. A. Raymond, J. Gamez, Stephan Arnold, A. DiGiovanni, J. Dalmau, C. C. Chari, H. F. Beer, J. C. Koetsier, J. Iriarte, E. Yunis, J. Casadevall, E. Le Guern, E. Stenager, S. R. Benbadis, J. M. Warter, F. Burklin, I. Theodorou, L. Johannesen, G. A. Graveland, X. Leclerc, I. Vecchio, L. Ozelius, G. Nicoletti, R. K. Gherardi, E. Esperet, M. L. Delodovici, F. Cattin, F. Paiau, Giorgio Sacilotto, C. A. J. Broere, D. Chavdarov, J. P. Willmer, C. H. Hawkes, Th. Naegele, E. Ellie, E. Dartigues, M. J. Guardiola, S. Hesse, Z. Levic, Marco Rovaris, P. Saugeir-Veber, B. A. Yaqub, H. F. Durwen, R. Larumbe, J. Ballabrina, M. Sendtner, J. Röther, M. Horstink, C. Kluglein, M.P. Montesi, H. Apaydin, J. Montoya, E. Waubant, Ch. Verellen-Dunoulin, A. Nicolai, J. Lopez-Delval, R. Lemon, G. Cantinho, E. Granieri, A. Zeviani, Wolfgang H. Oertel, U. Ficola, V. Di Piero, V. Fragola, K. Sabev, M. V. Guitera, I. Turki, F. Bolgert, P. Ingrand, J. M. Gobernado, L. M. E. Grimaldi, S. Baybas, B. Eymard, Y. Rolland, Y. Robitaille, Ta. Pampols, P. J. Koehler, A. Carroacedo, J. Vilchez, S. Di Vittorio, I. R. Rise, T. Nagy, M. Kuffner, E. Palazzini, A. Ott, J. Pruim, T. X. Arbizu, E. Manetti, C. Cervera, S. Felber, G. Gursoy, J. Scholz, G. A. Buscaino, M. S. Chen, A. Pascual, J. Hazan, J. U. Gajda, J. G. Cea, G. Bottini, G. Damalik, F. Le Doze, G. Bonaldi, J. M. Hew, C. Messina, A. M. Kennedy, J. M. Carney, N. M. F. Murray, M. Parent, M. Koepp, V. Dimova, D. De Leo, K. Jellinger, G. Salemi, S. Mientus, M. L. Hansen, F. Mazzucchelli, J. Vieth, M. Mauri, E. Bartels, L. Johannsen, C. Humphreys, J. Emile, D. N. Landon, E. Kansu, R. Sanchez-Pernaute, Rsj Frackowiak, M. Gonzalez Torres, L. Oller, C. Machedo, J. Kother, M. Billiard, H. Durak, T. Schindler, A. Frank, A. Uncini, A. Sbriccoli, C. Farinas, D. W. Paty, N. Fast, A. T. Zangaladze, A. Kerkhofs, J. M. Pino Garcia, I. De la Fuente, B. Marini, L. Gomez, I. Rubio, Alessandra Bardoni, C. Brodie, P. Acin, U. Sliwka, S. A. Hawkins, S. Tardieu, F. Vitullo, J. M. Pereira Monteino, R. Gagliardi, T. Jezewski, A. Cano, T. Lempert, F. Abad Alegria, G. Rotondo, D. Ince, C. Martinez Parra, Y. Huang, H. Luders, Y. Steinvil, F. G. A. Van Der Meche, R. Bianchi, A. Sanchez, T. Sevilla, J. M. Ketelslegers, A. Domzal-Stryga, M. Pandolfo, M. O. Josse, K. W. Neff, I. Blanco, G. W. Bruyn, O. W. Witte, J. L. Thibault, G. Andersen, J. Pariset, A. Marcone, R. J. M. Lane, A. Hofman, M. Verin, T. Matilla, P. Bedoucha, J. Roche, M. Lai, M. Collard, A. Ugarte, F. Gallecho, D. Silbersweig, C. Kennard, J. P. Azulay, T. W. Ho, P. L. I. Dellemijn, R. Girardello, F. Baas, B. Voss, F. Rozenberg, E. M. Brocker, V. Stanev, A. A. J. Soeterboek, A. Marra, A. Rey, E. Ertem, M. Sawradewicz-Rybak, J. De Keyser, P. Cavallari, F. Proust, Y. Chevalier, H. C. Hansen, D. Leys, C. A. Davie, K. Hoang-Xuan, C. Bairati, H. van Crevel, Thomas T. Warner, B. Bompais, A. Dobbeleir, T Campbell, C. Macko, C. J. M. Klijn, M. Dussallant, T. P. Berlit, W. Rozenbaum, M. J. van den Bent, W. A. Rocca, M. Muller, H. Hundemer, U. Zifko, M. Campera, F. Drislane, D. Ranoux, T. M. Kloss, Anil Kumar, I. Ruolt, C. Bargnani, B. Marescau, N. A. Losseff, S. Notermans, B. Kint, E. T. Burke, C. Aykut, J. Matias Guiu, P. Maquet, T. Drogendijk, M. Leone, K. von Ammon, M. Pepeliarska, C. Prados, L. DiGiamberardino, T. Logtenberg, G. Lenoir, I. Castaldo, Damhaut, M. Radionova, G. Sirabian, R. Navon, Giovanni Antonini, K. Al Moutaery, E. Chamas, R. Schönhuber, M. Giannini, B. Debilly, I. Labatut, H. Henon, J. A. Egido, M. Baudrimont, J. N. Lorenzo, J. E. C. Bromberg, R. Antonacci, J. J. Vilchez, T. Moulin, B. Rautenstrauss, Giovanni Meola, J. Noth, S Mammi, P. Laforet, F. Lopez, C. Gehring, S. Bort, G. Rancurel, D. Decamps, S. Kostadinova, Y. Shapira, B. Neundoerfer, D. Chavrot, M. Solimena, J. P. Salier, W. Deberdt, R. Hoff-Jörgensen, A. Messina, S. Meairs, G. Rosoklija, E. Nelis, I. Bertran, C. Ertekin, J. Lohmeyer, Mitermayer Galvao dos Reis, L. Calo, E. Maccagnano, A. P. Hays, J. Verlooy, M. G. Forno, T. Blanco, L. Bail, Gabriella Silvestri, J. Montero, F. Bertrand, R. T. Ghnassia, C. Besses, T. Sereghy, F. Shalit, G. Bogliun, S. Braghi, St. Baykouchev, C. Franke, A. Lasa, L. C. Archard, J. Kriebel, S. Shaunak, M. Nocito, Alexander Tsiskaridze, E. Manfredini, T. Seigal, David G. Gadian, M. Barlas, J. D. Degos, C. Seeber, J. Caemert, J. L. Mas, R. B. Pepinsky, M. G. D'Angelo, N. Baumann, S. Yorifuji, H. P. Endtz, M. A. Cassatella, R. A. C. Hughes, V. Golzi, A. Bittencourt, A. Ferreira, M. Sanson, C. Alper, M. Vermeulen, M. A. A. van Walderveen, E. Alexiou, C. H. Lucas, M. Fiorelli, Y. N. Debbink, R. Gil, S. Congia, T. Banerjee, J. M. Bouchard, A. N. Pinto, A. Ceballos-Baumann, G. Grollier, P. I. M. Schmitz, M. D. Catata, N. Lahat, N. S. Rao, P. Papathanasopoulos, J. Valls-Solé, D. Claus, G. Schroter, A. Castro, C. Videbaek, R. Martinez Dreke, A. D. Platts, M. Hermesl, A. C. PeÇanha-Martins, M. Cardoso Silva, P. Masnou, M. J. A. Tanner, Ch. Confavreux, B. Mishu, H. Rasmussen, L. Valenciano, Carlo Pozzilli, S. W. Li, V. Salzman, Y. Vashtang, Massimo Franceschi, M. Severo, G. Deuschl, S. Setien, G. Mariani, A. Protti, J. Castillo, M. J. B. Taphoorn, M. Frontali, I. Milonas, D. Decoq, J. A. Navarro, S. Castellvi-Pel, C. Ertikin, M. Urtasun, Y. Lajat, B. E. Kendall, E. Verdu, B. Gueguen, E. Boisen, R. Couderc, A Danek, JM Stevens, F. Nicoli, L. Feltri, M. L. Vazquez-Andre, J. A. Morgan-Hughes, L. D'Angelo, F. Y. Liew, L. F. Pascual, J. Patrignani Ochoa, Vittorio Martinelli, J. Cophignon, L. Zhang, S. Martin, J. F. Meder, H. C. Buschmann, L. Bertin, J. van Gijn, A. Barreiro, A. Cools, C. Leon, A. Berod, E. A. Anllo, E. Zanette, L. Petrov, R. Barona, B. Gallicchio, P. J. Cozzone, N. Diederich, G. Cancel, L. Schelosky, P. Orizaola, K. Yulug, S. Ozer, Valeria A. Sansone, B. Guiraud-Chaumeil, K. Voigt, P. Labauge, M. Eoli, J. Zhu, J. Aguirre, M. Ferrarini, B. Zyluk, E. Planas, A. Cadilha, C. Tortorella, H. Bismuth, C. E. Counsell, A. Laun, A. Ferlini, Rio J. Montalban, N. Biary, L. Becker, M. Fardeau, M. Poloni, V. M. S. de Bruin, C. Fornada, J. Barros, E. Ganzmann, E. Touze, D. Wallach, J. Peila, H. Fujimura, M. T. Iba-Zizen, G. Macchi, C. Villoslada, R. Gouider, Ph. Rondepierre, P. Grummich, P. Chiodi, C. Conte, M. Michels, P. Annunziata, G. Semana, C. Sommer, J. Vajsar, D. Zekin, J. Kulisevsky, David G. Munoz, B. Jacotot, M. 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Riva, M. H. Mahagne, M. Ozturk, Ve. Drory, N. Konic, C. Jungreis, A. Pou Serradell, J. L. Gauvrit, G. J. Chelune, S. Hermandez, T. Dingus, L. Hewer, Ch. Koch, M. N. Metz-Lutz, G. Parlato, M. Sinaki, Charles Pierrot-Deseilligny, H. C. Diener, J. Broeckx, J. Weill-Fulazza, M. L. Villar, M. Rizzo, O. Ganslandt, C. Duran, N. A. Fletcher, G. Di Giovacchino, Susan T. Iannaccone, C. Kolig, N. Fabre, H. A. Crockard, Rita Bella, M. Tazir, E. Papagiannuli, K. Overgaard, Emma Ciafaloni, I. Lorenzetti, F. Viader, P. A. H. Millac, I. Montiel, L. H. Visser, M. Palomar, P. L. Murgia, H. Pedersen, Rafael Blesa, S. Seddigh, W. O. Renier, I. Lemahieu, H. M. L. Jansen, L. Rosin, J. Galofre, K. Mattos, M. Pondal, G. M. Hadjigeorgiou, D. Francis, L. Cantin, D. Stegeman, M. Rango, A. B. M. F. Karim, S. Schraff, B. Castellotti, I. Iriarte, E. Laborde, T. J. Tjan, R. Mutani, D. Toni, B. Bergaasco, J. G. Young, C. Klotzsch, A. Zincone, X. Ducrocq, M. Uchuya, O. J. Kolar, A. Quattrone, T. Bauermann, Nereo Bresolin, J. Vallée, B. C. Jacobs, A. Campos, Werner Poewe, J. A. Villanueva, A. W. Kornhuber, A. Malafosse, E. Diez-Tejedor, G. Jungreia, M. J. A. Puchner, A. Komiyama, O. Saribas, V. Volpini, L. Geremia, S. Bressi, A. Nibbio, Timothy E. Bates, T. z. Tzonev, E. Ideman, G. A. Damlacik, G. Martino, G. Crepaldi, T. Martino, Kjell Någren, E. Idiman, D. Samuel, J. M. Perez Trullen, Y. van der Graaf, J. O. Thorell, M. J. M. Dupuis, E. Sieber, R. D'Alessandro, C. Cazzaniga, J. Faiss, A. Tanguy, A. Schick, I. Hoksergen, A. Cardozo, R. Shakarishvili, G. K. Wennlng, J. L. Marti-Vilalta, J. Weissenbach, I. L. Simone, Amalia C. Bruni, Darius J. Adams, C. Weiller, A. Pietrangeli, F. Croria, C. Vigo-Pelfrey, Patricia Limousin, A. Ducros, G. Conti, O. Lindvall, E. Richter, M. Zuffi, A. Nappo, T. Riise, J. Wijdenes, M. J. Fernandez, J. Rosell, P. Vermersh, S. Servidei, M. S. C. Verdugo, F. Gouttiere, W. Solbach, M. Malbezin, I. S. Watanabe, A. Tumac, W. I. McDonald, D. A. Butterfield, P. P. Costa, F. deRino, F. Bamonti, J. M. Cesar, C. H. Lahoz, I. Mosely, M. Starck, M. H. Lemaitre, K. M. Stephan, S. Tex, R. Bokonjic, I. Mollee, L. Pastena, M. Gutierrez, F. Boiler, M. C. Martinez-Para, M. Velicogna, O. Obuz, A. Grinspan, M. Guarino, L. M. Cartier, E. Ruiz, D. Gambi, S. Messina, M. Villa, Michael G. Hanna, J. Valk, Leone Pascual, M. Clanet, Z. Argov, B. Ryniewicz, E. Magni, B. Berlanga, K. S. Wong, C. Gellera, C. Prevost, F. Gonzalez-Huix, R. Petraroli, J. E. G. Benedikz, I. Kojder, C. Bommelaer, L. Perusse, M. R. Bangioanni, Guy M. McKhann, A. Molina, C. Fresquet, E. Sindern, Florence Pasquier, M. J. Rosas, M. Altieri, O. Simoncini, M. Koutroumanidis, C. A. F. Tulleken, M. Dary-Auriol, S. Oueslati, H. Kruyer, I. Nishisho, C. R. Horning, A. Vital, G. V. Czettritz, J. Ph. Neau, B. Mihout, A. Ameri, M. Francis, S. Quasthoff, D. Taussig, S. Blunt, P. Valentin, C. Y. Gao, O. Heinzlef, H. d'Allens, C. Coudero, M. Erfas, G. Borghero, P. J. Modrego Pardo, M. C. Patrosso, N. L. Gershfeld, P. A. J. M. Boon, O. Sabouraud, M. Lara, J. Svennevig, G. L. Lenzi, A. Barrio, H. Villaroya, JosÇ M. Manubens, O. Boespflug-Tanguy, M. Carreras, D. A. Costiga, J. P. Breux, S. Lynn, C. Oliveras Ley, A. G. Herbaut, J. Nos, C. Tornali, Y. A. Hekster, J. L. Chopard, J. M. Manubens, P. Chemouilli, A. Jovicic, F. Dworzak, S. Smirne, S. E. Soudain, B. Gallano, D. Lubach, G. Masullo, G. Izquierdo, A. Pascual Leone Pascual, A. Sessa, V. Freitas, O. Crambes, L. Ouss, G. W. Van Dijk, P. Marchettini, P. Confalonieri, M. Donaghy, A. Munnich, M. Corbo, and M. E. L. van der Burg
Subjects: Neurology, business.industry, Media studies, Library science, Medicine, Neurology (clinical), business
Published: 1994
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29. Abstracts

Author: J. M. Derlon, M. C. Petit-taboué, F. Dauphin, P. Courtheoux, F. Chapon, P. Creissard, F. Darcel, J. P. Houtteville, B. Kaschten, B. Sadzot, A. Stevenaert, Juri G. Tjuvajev, Homer A. Macapinlac, Farhad Daghighian, James Z. Ginos, Ronald D. Finn, M. S. Jiaju Zhang, Bradley Beattie, Martin Graham, Steven M. Larson, Ronald G. Blasberg, M. Levivier, S. Goldman, B. Pirotte, J. M. Brucher, D. Balériaux, A. Luxen, J. Hildebrand, J. Brotchi, K. G. Go, R. L. Kamman, E. L. Mooyaart, M. A. A. M. Heesters, P. E. Sijens, M. Oudksrk, P. van Dijk, P. C. Levendag, Ch. J. Vecht, R. J. Metz, D. N. Kennedy, B. R. Rosen, F. H. Hochberg, A. J. Fishman, P. A. Filipek, V. S. Caviness, M. W. Gross, F. X. Weinzierl, A. E. Trappe, W. E. Goebel, A. M. Frank, Georg Becker, Andreas Krone, Karsten Schmidt, Erich Hofmann, Ulrich Bogdahn, H. Bencsch, S. Fclber, G. Finkenstedt, C. Kremser, G. Sfockhammer, F. Aichner, U. Bogdahn, T. Fröhlich, G. Becker, A. Krone, R. Schlief, J. Schürmann, P. Jachimczak, E. Hofmann, W. Roggendorf, K. Roosen, C. M. Carapella, G. Carpinelli, R. Passalacqua, L. Raus, M. Giannini, R. Mastrostefano, F. Podo, A. Tofani, R. Maslrostefano, M. Mottoles, A. Ferraironi, M. G. Scelsa, P. Oppido, A. Riccio, C. L. Maini, L. Collombier, L. Taillandier, M. Dcbouverie, M. H. Laurens, P. Thouvenot, M. Weber, A. Bertrand, G. S. Cruickshank, J. Patterson, D. Hadley, Olivier De Witte, Jerzy Hildebrand, André Luxen, Serge Goldman, R. -I. Ernestus, K. Bockhorst, M. Eis, T. Els, M. Hoehn-Berlage, M. Gliese, R. Fründ, A. Geissler, C. Woertgen, M. Holzschuh, O. Hausmann, A. Merlo, E. Jerrnann, J. Uirich, R. Chiquet-Ehrismann, J. Müller, H. Mäcke, O. Gratzl, K. Herholz, M. Ghaemi, M. Würker, U. Pietrzyk, W. -D. Heiss, K. Kotitschke, M. Brandl, J. C. Tonn, A. Haase, S. Muigg, S. Felber, M. Woydt, Heinrich Lanfermann, Walter Heindel, Harald Kugel, Ralf -Ingo Erneslus, Gabricle Röhn, Klaus Lackner, F. S. Pardo, S. Kutke, A. G. Sorensen, L. L. Mechtler, S. Withiam-Lench, K. Shin, W. R. Klnkel, M. Patel, B. Truax, P. Kinkel, L. Mechtler, M. Ricci, P. Pantano, A. Maleci, S. Pierallini, D. Di Stefano, L. Bozzao, G. P. Cantore, Gabriele Röhn, R. Schröder, R. Ruda, C. Mocellini, R. Soffietti, M. Campana, R. Ropolo, A. Riva, P. G. de Filippi, D. Schiffer, D. Salgado, M. Rodrigues, L. Salgado, A. T. Fonseca, M. R. Vieira, J. M. Bravo Marques, H. Satoh, T. Uozumi, K. Kiya, K. Kurisu, K. Arita, M. Sumida, F. Ikawa, Tz. Tzuk-Shina, J. M. Gomori, R. Rubinstein, A. Lossos, T. Siegal, W. Vaalburg, A. M. J. Paans, A. T. M. Willemsen, A. van Waarde, J. Pruim, G. M. Visser, S. Valentini, Y. L. T. Ting, R. De Rose, G. Chidichimo, G. Corricro, Karin van Lcycn-Pilgram, Ralf -Ingo Erncslus, Norfried Klug, K. van Leyen-Pilgram, N. Klug, U. Neumann, Karl H. Plate, Georg Breier, Birgit Millaucr, Herbert A. Weich, Axel Ullrich, Werner Risau, N. Roosen, R. K. Chopra, T. Mikkelsen, S. D. Rosenblum, P. S. Yan, R. Knight, J. Windham, M. L. Rosenblum, A. Attanasio, P. Cavalla, A. Chio, M. T. Giordana, A. Migheli, V. Amberger, T. Hensel, M. E. Schwab, Luigi Cervoni, Paolo Celli, Roberto Tarantino, C. Huettner, U. Berweiler, I. Salmon, S. Rorive, K. Rombaut, J. Haot, R. Kiss, C. Maugard-Louboutin, J. Charrier, G. Fayet, C. Sagan, P. Cuillioere, G. Ricolleau, S. Martin, D. Menegalli-Bogeelli, Y. Lajat, F. Resche, Péter Molnàr, Helga Bárdos, Róza Ádány, J. P. Rogers, G. J. Pilkington, B. Pollo, G. Giaccone, A. Allegranza, O. Bugiani, J. Prim, J. Badia, E. Ribas, F. Coello, E. Shezen, O. Abramsky, M. Scerrati, R. Roselli, M. Iacoangeli, A. Pompucci, G. F. Rossi, Saleh M. Al. Deeb, Osama Koreich, Basim Yaqub, Khalaf R. Al. Moutaery, S. Marino, M. C. Vigliani, V. Deburghgraeve, D. Gedouin, M. Ben Hassel, Y. Guegan, B. Jeremic, D. Grujicic, V. Antunovic, M. Matovic, Y. Shibamoto, Merja Kallio, Helena Huhmar, Ch. Kudoh, A. Detta, K. Sugiura, E. R. Hitchcock, R. Di Russo, M. Cipriani§, E. M. Occhipinti, E. M. S. Conti, A. Clowegeser, M. Ortler, M. Seiwald, H. Kostron, B. Rajan, G. Ross, C. Lim, S. Ashlcy, D. Goode, D. Traish, M. Brada, G. A. C. vd Sanden, L. J. Schouten, J. W. W. Coebergh, P. P. A. Razenberg, A. Twijnstra, A. Snilders-Keilholz, J. H. C. Voormolen, J. Hermans, J. W. H. Leer, F. Baylac, M. Dcbouvcrie, R. Anxionnal, S. Bracard, J. M. Vignand, A. Duprcz, M. Winking, D. K. Böker, T. Simmet, David Rothbart, John Strugar, Jeroen Balledux, Gregory R. Criscuolo, Piotr Jachimczak, Armin Blesch, Birgit Heβdörfer, Ralf -Ingo Ernestus, Roland Schröder, Norfrid Klug, H. G. J. Krouwer, S. G. v. Duinen, A. Algra, J. Zentner, H. K. Wolf, B. Ostertun, A. Hufnagel, M. G. Campos, L. Solymosi, J. Schramm, E. S. Newlands, S. M. O'Reilly, M. Brampton, R. Sciolla, D. Seliak, R. Henriksson, A. T. Bergenheim, P. Björk, P. -O. Gunnarsson, Ml. Hariz, R. Grant, D. Collie, A. Gregor, K. P. Ebmeier, G. Jarvis, F. Lander, A. Cull, R. Sellar, C. Thomas, S. Elyan, F. Hines, S. Ashley, S. Stenning, J. J. Bernstein, W. J. Goldberg, U. Roelcke, K. Von Ammon, E. W. Radu, D. Kaech, K. L. Leenders, M. M. Fitzek, J. Efird Aronen, F. Hochberg, M. Gruber, E. Schmidt, B. Rosen, A. Flschman, P. Pardo, U. M. U. Afra, L. Sipos, F. Slouik, A. Boiardi, A. Salmaggi, A. Pozzi, L. Farinotti, L. Fariselli, A. Silvani, A. Brandes, E. Scelzi, A. Rigon, P. Zampieri, M. Pignataro, P. D'. Amanzo, P. Amista, A. Rotilio, M. V. Fiorentino, R. Thomas, L. Brazil, A. M. O'Connor, Maurizio Salvati, Fabrizio Puzzilli, Michele Raguso, R. Duckworth, R. Rumpling, M. Rottuci, G. Broggi, N. G. Plrint, E. Sabattini, V. Manetto, H. Gambacorta, S. Poggi, S. Pileri, R. Ferracini, D. V. Plev, N. J. Hopf, E. Knosp, J. Bohl, A. Perncczky, I. Catnby, O. Dewitte, J. L. Pasteels, I. Camby, F. Darro, A. Danguy, M. C. Kiu, G. M. Lai, T. S. Yang, K. T. Ng, J. S. Chen, C. N. Chang, W. M. Leung, Y. S. Ho, M. Deblec Rychter, A. Klimek, P. P. Liberski, A. Karpinaka, P. Krauseneck, V. Schöffel, B. Müller, F. W. Kreth, M. Faist, P. C. Warnke, C. B. Ostertag, K. M. B. v. Nielen, M. C. Visscr, C. Lebrun, M. Lonjon, T. Desjardin, J. F. Michiels, Sa. Lagrange J. L. Chanalet, J. L. Roche, M. Chatel, L. Mastronardi, F. Puzzilli, Farah J. Osman, P. Lunardi, M. Matsutani, Y. Ushio, K. Takakura, Johan Menten, Han Hamers, Jacques Ribot, René Dom, Hans Tcepen, N. Weidner, G. Naujocks, D. van Roost, O. D. Wiestler, A. Kuncz, C. Nieder, M. Setzel-Sesterhein, M. Niewald, I. Schnabel, K. S. O'Neill, N. D. Kitchen, P. R. Wilkins, H. T. Marsh, E. Pierce, R. Doshi, R. Deane, S. Previtali, A. Quattrini, R. Nemni, A. Ducati, L. Wrabetz, N. Canal, C. J. A. Punt, L. Stamatakis, B. Giroux, E. Rutten, Matthew R. Quigley, P. A. -C. Beth Sargent, Nicholas Flores, Sheryl Simon, Joseph C. Maroon, A. A. Rocca, C. Gervasoni, A. Castagna, P. Picozzi, E. Giugni, G. P. Tonnarelli, F. Mangili, G. Truci, M. Giovanelli, W. Sachsenheimer, T. Bimmler, H. Rhomberg W. Eiter, A. Obwegesser, H. Steilen, W. Henn, J. R. Moringlane, H. Kolles, W. Feiden, K. D. Zang, W. I. Sleudel, Andreas Steinbrecher, Martin Schabet, Clemens Heb, Michael Bamberg, Johannes Dichgans, G. Stragliotto, J. Y. Delattre, M. Poisson, L. Tosatto, P. D'Amanzo, N. Menicucci, S. Mingrino, W. I. Steudel, R. Feld, J. Ph. Maire, M. Caudry, J. Guerin, D. Celerier, N. Salem, H. Demeaux, J. F. Fahregat, M. E. Kusak, A. Bucno, J. Albisua, P. Jerez, J. L. Sarasa, R. Garefa, J. M. de Campos, A. Bueno, R. García-Delgado, R. García-Sola, A. A. Lantsov, T. I. Shustova, D. Lcnartz, R. Wellenreuther, A. von Deirnling, W. Köning, J. Menzel, S. Scarpa, A. Manna, M. G. Reale, P. A. Oppido, L. Frati, C. A. Valery, M. Ichen, J. P. Foncin, C. Soubrane, D. Khayat, J. Philippon, R. Vaz, C. Cruz, S. Weis, D. Protopapa, R. März, P. A. Winkler, H. J. Reulen, K. Bise, E. Beuls, J. Berg, W. Deinsberger, M. Samii, V. Darrouzet, J. Guérin, R. Trouette, N. Causse, J. P. Bébéar, F. Parker, J. N. Vallee, R. Carlier, M. Zerah, C. Lacroix-Jousselin, Joseph M. Piepmeier, John Kveton, Agnes Czibulka, G. S. Tigliev, M. P. Chernov, L. N. Maslova, José M. Valdueza, Werner Jänisch, Alexander Bock, Lutz Harms, E. M. Bessell, F. Graus, J. Punt, J. Firth, T. Hope, Osama Koriech, Saleh Al Deeb, Khalaf Al Moutaery, B. Yaqub, A. Franzini, R. Goldbrunner, M. Warmuth-Metz, W. Paulus, J. -Ch. Tonn, I. I. Strik, C. Markert, K. -W. Pflughaupt, B. P. O'Neill, R. P. Dinapoli, J. Voges, V. Sturm, U. Deuß, C. Traud, H. Treuer, R. Lehrke, D. G. Kim, R. P. Müller, Yu. S. Alexandrov, K. Moutaery, M. Aabed, O. Koreich, G. M. Ross, D. Ford, I. L. O. Schmeets, J. J. Jager, M. A. G. Pannebakker, J. M. A. de Jong, E. van Lindert, K. Kitz, S. Blond, F. Dubois, R. Assaker, M. C. Baranzelli, M. Sleiman, J. P. Pruvo, B. Coche-Dequeant, K. Sano, G. PetriČ-Grabnar, B. Jereb, N. Župančič, M. Koršič, N. G. Rainov, W. Burkert, Yukitaka Ushio, Masato Kochi, Youichi Itoyama, R. García, L. Ferrando, K. Hoang-Xuan, M. Sanson, P. Merel, O. Delattre, G. Thomas, D. Haritz, B. Obersen, F. Grochulla, D. Gabel, K. Haselsberger, H. Radner, G. Pendl, R. W. Laing, A. P. Warrington, P. J. C. M. Nowak, I. K. K. Kolkman-Deurloo, A. G. Visser, Hv. d. Berge, C. G. J. H. Niël, P. Bergström, M. Hariz, P. -O. Löfroth, T. Bergenheim, C. Cortet-rudelli, D. Dewailly, B. Coche-dequeant, B. Castelain, R. Dinapoli, E. Shaw, R. Coffey, J. Earle, R. Foote, P. Schomberg, D. Gorman, N. Girard, M. N. Courel, B. Delpech, G. M. Friehs, O. Schröttner, R. Pötter, R. hawliczek, P. Sperveslage, F. J. Prott, S. Wachter, K. Dieckmann, B. Bauer, R. Jund, F. Zimmermann, H. J. Feldmann, P. Kneschaurek, M. Molls, G. Lederman, J. Lowry, S. Wertheim, L. Voulsinas, M. Fine, I. Voutsinas, G. Qian, H. Rashid, P. Montemaggi, R. Trignani, C. West, W. Grand, C. Sibata, D. Guerrero, N. James, R. Bramer, H. Pahlke, N. Banik, M. Hövels, H. J. J. A. Bernsen, P. F. J. W. Rijken, B. P. J. Van der Sanden, N. E. M. Hagemeier, A. J. Van der Kogel, P. J. Koehler, H. Verbiest, J. Jager, A. McIlwrath, R. Brown, C. Mottolesb, A. Pierre'Kahn, M. Croux, J. Marchai, P. Delhemes, M. Tremoulet, B. Stilhart, J. Chazai, P. Caillaud, R. Ravon, J. Passacha, E. Bouffet, C. M. F. Dirven, J. J. A. Mooy, W. M. Molenaar, G. M. Lewandowicz, N. Grant, W. Harkness, R. Hayward, D. G. T. Thomas, J. L. Darling, N. Delepine, I. I. Subovici, B. Cornille, S. Markowska, JC. Desbois Alkallaf, J. KühI, D. Niethammer, H. J. Spaar, A. Gnekow, W. Havers, F. Berthold, N. Graf, F. Lampert, E. Maass, R. Mertens, V. Schöck, A. Aguzzi, A. Boukhny, S. Smirtukov, A. Prityko, B. Hoiodov, O. Geludkova, A. Nikanorov, P. Levin, B. D'haen, F. Van Calenbergh, P. Casaer, R. Dom, J. Menten, J. Goffin, C. Plets, A. Hertel, P. Hernaiz, C. Seipp, K. Siegler, R. P. Baum, F. D. Maul, D. Schwabe, G. Jacobi, B. Kornhuber, G. Hör, A. Merzak, H. K. Rooprai, P. Bullock, P. H. M. F. van Domburg, P. Wesseling, H. O. M. Thijssen, J. E. A. Wolff, J. Boos, K. H. Krähling, V. Gressner-Brocks, H. Jürgens, J. Schlegel, H. Scherthan, N. Arens, Gabi Stumm, Marika Kiessling, S. Koochekpour, G. Reifenberger, J. Reifenberger, L. Liu, C. D. James, W. Wechsler, V. P. Collins, Klaus Fabel-Schulte, Plotr Jachimczak, Birgitt Heßdörfer, Inge Baur, Karl -Hermann Schlingensiepen, Wolgang Brysch, A. Blesch, A. K. Bosserhoff, R. Apfel, F. Lottspeich, R. Büttner, R. Cece, I. Barajon, S. Tazzari, G. Cavaletti, L. Torri-Tarelli, G. Tredici, B. Hecht, C. Turc-Carel, R. Atllas, P. Gaudray, J. Gioanni, F. Hecht, J. A. Rey, M. J. Bello, M. Parent, P. Gosselin, J. L. Christiaens, J. R. Schaudies, M. Janka, U. Fischer, E. Meese, M. Remmelink, P. Cras, R. J. Bensadoun, M. Frenay, J. L. Formento, G. Milano, J. L. Lagrange, P. Grellier, J. -Y. Lee, H. -H. Riese, J. Cervós-Navarro, W. Reutter, B. Lippitz, C. Scheitinger, M. Scholz, J. Weis, J. M. Gilsbach, L. Füzesi, Y. J. Li, R. Hamelin, Erik Van de Kelft, Erna Dams, Jean -Jacques Martin, Patrick Willems, J. Erdmann, R. E. Wurm, S. Sardell, J. D. Graham, Jun -ichi Kuratsu, M. Aichholzer, K. Rössler, F. Alesch, A. Ertl, P. S. Sorensen, S. Helweg-Larsen, H. Mourldsen, H. H. Hansen, S. Y. El Sharoum, M. W. Berfelo, P. H. M. H. Theunissen, I. Fedorcsák, I. Nyáry, É. Osztie, Á. Horvath, G. Kontra, J. Burgoni-chuzel, P. Paquis, SW. Hansen, PS. Sørensen, M. Morche, F. J. Lagerwaard, W. M. H. Eijkenboom, P. I. M. Schmilz, S. Lentzsch, F. Weber, J. Franke, B. Dörken, G. Schettini, R. Qasho, D. Garabello, S. Sales, R. De Lucchi, E. Vasario, X. Muracciole, J. Régis, L. Manera, J. C. Peragut, P. Juin, R. Sedan, K. Walter, K. Schnabel, N. Niewald, U. Nestle, W. Berberich, P. Oschmann, R. D. Theißen, K. H. Reuner, M. Kaps, W. Dorndorf, K. K. Martin, J. Akinwunmi, A. Kennedy, A. Linke, N. Ognjenovic, A. I. Svadovsky, V. V. Peresedov, A. A. Bulakov, M. Y. Butyalko, I. G. Zhirnova, D. A. Labunsky, V. V. Gnazdizky, I. V. Gannushkina, M. J. B. Taphoorn, R. Potman, F. Barkhof, J. G. Weerts, A. B. M. F. Karim, J. J. Heimans, M. van de Pol, V. C. van Aalst, J. T. Wilmink, J. J. van der Sande, W. Boogerd, R. Kröger, A. Jäger, C. Wismeth, A. Dekant, W. Brysch, K. H. Schlingensiepen, B. Pirolte, V. Cool, C. Gérard, J. L. Dargent, T. Velu, U. Herrlinger, M. Schabet, P. Ohneseit, R. Buchholz, Jianhong Zhu, Regina Reszka, Friedrich Weber, Wolfgang Walther, L. I. Zhang, Mario Brock, J. P. Rock, H. Zeng, J. Feng, J. D. Fenstermacher, A. Gabizon, M. Beljanski, S. Crochet, B. Zackrisson, J. Elfverson, G. Butti, R. Baetta, L. Magrassi, M. R. De Renzis, M. R. Soma, C. Davegna, S. Pezzotta, R. Paoletti, R. Fumagalli, L. Infuso, A. A. Sankar, G. -L. Defer, P. Brugières, F. Gray, C. Chomienne, J. Poirier, L. Degos, J. D. Degos, Bruno M. Colombo, Stefano DiDonato, Gaetano Finocchiaro, K. M. Hebeda, H. J. C. M. Sterenborg, A. E. Saarnak, J. G. Wolbers, M. J. C. van Gemert, P. Kaaijk, D. Troost, S. Leenstra, P. K. Das, D. A. Bosch, B. W. Hochleitner, A. Obwegeser, W. Vooys, G. C. de Gast, J. J. M. Marx, T. Menovsky, J. F. Beek, V. Schirrmacher, A. Schmitz, A. M. Eis-Hübinger, p. h. Piepmeier, Patricia Pedersen, Charles Greer, Tommy Shih, Amr Elrifal, William Rothfus, L. Rohertson, R. Rampling, T. L. Whoteley, J. A. Piumb, D. J. Kerr, P. A. Falina, I. M. Crossan, K. L. Ho, M. M. Ruchoux, S. Vincent, F. Jonca, J. Plouet, M. Lecomte, D. Samid, A. Thibault, Z. Ram, E. H. Oldfield, C. E. Myers, E. Reed, Y. Shoshan, Tz. Siegal, G. Stockhammer, M. Rosenblum, F. Lieberman, A. J. A. Terzis, R. Bjerkvig, O. D. Laerum, H. Arnold, W. D. Figg, G. Flux, S. Chittenden, P. Doshi, D. Bignor, M. Zalutsky, Juri Tjuvajev, Michael Kaplitt, Revathi Desai, M. S. Bradley, B. S. Bettie, Bernd Gansbacher, Ronald Blasberg, H. K. Haugland, J. Saraste, K. Rooseni, A. J. P. E. Vincent, C. J. J. Avezaat, A. Bout, J. L. Noteboom, C. h. Vecht, D. Valerio, P. M. Hoogerbrugge, R. Reszka, J. Zhu, W. Walther, J. List, W. Schulz, I. I. J. C. M. Sterenborg, W. Kamphorst, H. A. M. van Alplien, P. Salander, R. Laing, B. Schmidt, G. Grau, T. Bohnstedt, A. Frydrych, K. Franz, R. Lorenz, F. Berti, A. Paccagnella, P. L. van Deventer, P. L. I. Dellemijn, M. J. van den Bent, P. J. Kansen, N. G. Petruccioli, E. Cavalletti, B. Kiburg, L. J. Müller, C. M. Moorer-van Delft, H. H. Boer, A. Pace, L. Bove, A. Pietrangeli, P. Innocenti, A. Aloe, M. Nardi, B. Jandolo, S. J. Kellie, S. S. N. De Graaf, H. Bloemhof, D. Roebuck, Pozza L. Dalla, D. D. R. Uges, I. Johnston, M. Besser, R. A. Chaseling, S. Koeppen, S. Gründemann, M. Nitschke, P. Vieregge, E. Reusche, P. Rob, D. Kömpf, T. J. Postma, J. B. Vermorken, R. P. Rampling, D. J. Dunlop, M. S. Steward, S. M. Campbell, S. Roy, P. H. E. Hilkens, J. Verweij, W. L. J. van Putten, J. W. B. Moll, M. E. L. van der Burg, A. S. T. Planting, E. Wondrusch, U. Zifko, M. Drlicek, U. Liszka, W. Grisold, B. Fazeny, Ch. Dittrich, Jan J. Verschuuren, Patricio I. Meneses, Myrna R. Rosenfeld, Michael G. Kaplitt, Jerome B. Posner, Josep Dalmau, P. A. E. Sillevis Smitt, G. Manley, J. B. Posner, G. Bogliun, L. Margorati, G. Bianchi, U. Liska, B. Casati, C. Kolig, H. Grisold, R. Reñe, M. Uchuya, F. Valldeoriola, C. Benedetti de Cosentiro, D. Ortale, R. Martinez, J. Lambre, S. Cagnolati, C. Vinai, M. G. Forno, R. Luksch, P. Confalonieri, J. Scholz, G. Pfeiffer, J. Netzer, Ch. Hansen, Ch. Eggers, Ch. Hagel, K. Kunze, Marc K. Rosenblum, and Frank S. Lieberman
Subjects: Cancer Research, Neurology, Oncology, Neurology (clinical)
Published: 1994
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30. An improved method for the preparation of [11C]verapamil

Author: B. Maas, W Vaalburg, T Wegman, and Philippus Elsinga
Subjects: Mesylates, Methyl triflate, Radiochemistry, Radiation, Chemistry, Stereochemistry, Temperature, Total synthesis, Improved method, Reaction temperature, Verapamil, Drug Resistance, Neoplasm, Yield (chemistry), Methods, medicine, Humans, ATP Binding Cassette Transporter, Subfamily B, Member 1, Carbon Radioisotopes, Trifluoromethanesulfonate, Tomography, Emission-Computed, medicine.drug, Nuclear chemistry
Abstract: This paper describes an improved preparation of [11C]verapamil by reaction of [11C]methyl triflate with desmethylverapamil. The optimal reaction temperature, amount of precursor and reaction time were assessed. With this method [11C]verapamil can be prepared with a reproducible radiochemical yield of 66±4% (EOB, based on [11C]methyltriflate). Total synthesis time was 60 min. Radiochemical purity was >99% and specific activities varied between 5 and 30 TBq/mmol.
Published: 2002
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31. Abstracts of papers and posters Meeting on Pharmaceutical Sciences

Author: J. D. Vries, J. Zuidema, Trea A. Galiën, G. T. Werf, H. Wesseling, Herre Talsma, A. C. Eissens, Ilva Bommel, N. Stecher, C. M. Ree, M. Olling, B. Steffens, R. J. M. Hooff, K. S. Beuning, M. W. Lammers, W. I. Iwema Bakker, H. J. Haisma, D. A. Piers, A. N. Fransz, R. A. M. Kengen, P. Salomons, G. H. P. Wierik, Russell C. Coile, L. M. Bouter, Marco C. Stehouwer, J. Medema, J. G. W. Kosterink, W. N. E. Wolthuis, D. J. Touw, G. M. Visser, A. Dijk, D. R. A. Uges, Anke M. Trigtv, A. Knevelman, R. Stewart, H. Junginger, J. A. A. M. Kamps, H. E. Boddé, Jacobus Swart, J. R. Marler, Bruno H. Stricker, R. H. P. Smit, J. Biller, N. E. H. W. Hendrikx, Rein Vos, F. J. W. Mansvelt, S. S. N. Graaf, R. H. B. Meyboom, J. Hermans, W. Brand, E. J. F. Franssen, H. P. Adams, L. Leij, Hubert G. M. Leufkens, Ferd Sturmans, P. J. Reinhoud, I. H. Go, D. N. Reinhoudt, A. T. P. Skrabanja, J. W. F. Mil, M. M. W. B. Hendriks, H. S. Lau, T. Hultermans, A.J.M. Schoonen, R. Wolters, G. Storm, M. W. Versantvoort, L. J. Stokx, G. H. P. Koning, Albert Bakker, Anthonius Boer, J. Velden, B. A. Ruben, G. Luurtsema, W. E. Hennink, T. Beumer, A. H. P. Paes, H. G. M. Leufkens, C. Oussoren, R. J. Boskma, Peter W. Swaan, Nicolien Wieringa, de Dick Zeeuw, D. A. Bloemhof, B. Mevboom-de Jong, Ellis J. C. Boerkamp, K. J. C. Wientjes, G. Th. van der Werf, J. M. L. Engelen, E. R. Heerdink, J. E. Leysen, Anthonius de Boer, Inge H. Reuvers, D. de Boer, Yechiel A. Hekster, Auke Bult, Ron M. C. Herings, M. C. Cornel, C. Thomas, H. N. Magnani, P. M. L. A. Bemt, A. Schotte, H. A. Tissot van Patot, L. Veehof, E. C. A. Winden, Andrew Herxheimer, D. Shochat, D. Post, B. Struska, Harry Meinardi, P. H. Elsinga, H. Bloemhof, E. Postma-Lim, G. J. Driessen, R. M. E. Franssen, Donald R. A. Uges, J. H. Proost, Jennifer Heijman, J. Dijk, Arnold B. Bakker, L. M. L. Slolk, D. M. Barends, Henk Vos, J. C. Verhoef, Eric J. F. Franssen, Jenny Hettelaar, J. A. Leusink, Y. M. Groot-Padberg, M. J. Steenbergen, Margot Jeronimus-Stratingh, A. G. Rauws, H. G. A. Mokkink, L. E. Visser, L. Flendrig, W.H.M. Craane-van Hinsberg, H. R. M. Gorissen, M. Danhof, Eric J. C. Blok, P. Denig, L. T. W. Jong-van den Berg, P. F. M. Janssen, Hugo Paauw, F. J. Schmidt, H. Vromans, M. Foets, F. v. Dinther, T. F. J. Tromp, H. J. C. Wit, Cf Lerk, E. W. Massey, J. Fennis, E. W. M. Schrijnemakers, P. J. Swart, Miriam C. J. M. Sturkenboom, J. H. Beijnen, Jan I. Jmker, B. M. Jongh, W. Vaalburg, Eibert R. Heerdink, Flora M. Haaijer-Ruskamp, Daan J.A. Crommelin, M. Haas, F. W. J. Gribnau, B. J. Smit, J. J. H. Thijssen, M. Kuipers, Michiel H. De Vries, J. Raemaekers, C. E. M. Gelderen, F. W. Dijkers, A. M. Nijenhuis, Hubert G. Leufkens, Hans Kaldeway, Andries Bruins, D. K. F. Meijer, Miriam Mol, J. J. Tukker, Alma Middeibeek, John Urquhart, F. M. Haaijer-Ruskamp, Jan C. Reuyl, J. N. Davis, M. K. Casparie, M. H. Vingerhoeds, Floor Rikken, A. A. T. M. M. Vinks, A. Keyser, Jaap Willems, Lolkje T. W. de Jong-van den Berg, Albert Versluis, P. M. J. Stuvt, J. E. Nagtegaal, M. W. A. Jonge, J. M. K. H. Wierda, E. F. Smit, B. H. Ch. Stricker, Arijan J. Porsius, J. C. H. Borchert, J. W. Gubbels, S. W. F. Omta, G. L. Scherphof, H. Lier, K. Wiedhaup, D. K. F. Mijer, Max Maas, Jan W. Kijne, F. Iren, A. Kuijpers, J. Meulenbelt, H. G. M. Heijerman, Willy O. Renier, P. J. M. Kil, Jrbj Brouwers, E. T. J. Peters, Dick F. J. Tromp, Wim Vaalburg, Geb Visser, Lolkie T. W. Jong vd Berg, M. C. J. M. Sturkenboom, Gert Luurtsema, W. Bakker, and C. Florax
Subjects: Pharmacology, Engineering, Medical education, business.industry, Pharmaceutical Science, Pharmacology (medical), Pharmacy, General Medicine, Pharmaceutical sciences, Toxicology, business
Published: 1993
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32. Synthesis and evaluation of [18F]fluoroethyl SA4503 and SA5845 as pet-ligands for the sigma receptor

Author: W Vaalburg, Kiichi Ishiwata, Philippus Elsinga, Tadayuki Kobayashi, Kazunori Kawamura, Michio Senda, and Hideo Tsukada
Subjects: Stereochemistry, Chemistry, Organic Chemistry, Drug Discovery, Sigma receptor, Radiology, Nuclear Medicine and imaging, Biochemistry, Spectroscopy, Fluoroethyl, Analytical Chemistry
Published: 2001
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33. Labeling of cyclooxygenase-2 inhibitors DuP-697 and its desbromo derivative: The crucial role of the solvent

Author: E. F. J. de Vries and W Vaalburg
Subjects: biology, Stereochemistry, Organic Chemistry, Prostaglandin, Biochemistry, Analytical Chemistry, Solvent, chemistry.chemical_compound, chemistry, Drug Discovery, dup, biology.protein, Radiology, Nuclear Medicine and imaging, Cyclooxygenase, Solvent effects, Spectroscopy, Derivative (chemistry)
Published: 2001
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34. Novel oxidation methods of [11C]carbon monoxide and [11C]methane on Fe/ZSM-5 zeolite

Author: Zoltán Kovács, É. Sarkadi-Priboczki, Philippus Elsinga, W. Vaalburg, Géza Horváth, and J. Medema
Subjects: chemistry.chemical_compound, Chemistry, Organic Chemistry, Drug Discovery, Inorganic chemistry, Radiology, Nuclear Medicine and imaging, Biochemistry, Spectroscopy, Methane, ZSM-5 zeolite, Analytical Chemistry, Carbon monoxide
Published: 2001
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35. The use of a zymark robotic system as a multitracer synthesizer

Author: J. Mederna, Philippus Elsinga, W Vaalburg, L. Eriks‐Fluks, and E. F. J. de Vries
Subjects: Robotic systems, Chemistry, business.industry, Organic Chemistry, Drug Discovery, Radiology, Nuclear Medicine and imaging, Control engineering, Robotics, Artificial intelligence, business, Biochemistry, Spectroscopy, Analytical Chemistry
Published: 2001
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36. Survey of fluorine-18 labeled synthons as alkylating agents for the radiolabeling of (OLIGO)nucleotides

Author: E. F. J. de Vries, J. Veenstra, Philippus Elsinga, and W Vaalburg
Subjects: chemistry.chemical_classification, Stereochemistry, Organic Chemistry, Synthon, chemistry.chemical_element, Alkylation, Biochemistry, Analytical Chemistry, chemistry, Drug Discovery, Fluorine, Organic chemistry, Radiology, Nuclear Medicine and imaging, Nucleotide, Spectroscopy
Published: 2001
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37. Synthesis and evaluation of radiolabelled antagonists for beta-adrenoceptor imaging in the brain with pet

Author: T Wegman, W Vaalburg, B. Maas, Philippus Elsinga, P Doze, and A. van Waarde
Subjects: β adrenoceptor, Chemistry, Organic Chemistry, Drug Discovery, Radiology, Nuclear Medicine and imaging, Pharmacology, Beta adrenoceptor, Biochemistry, Spectroscopy, Analytical Chemistry
Published: 2001
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38. Unexpected substituent effects in the labeling of fluoroquinolone antimicrobal agents with fluorine-18

Author: W Vaalburg, K. Hirokawa, M. Yamaguchi, E. F. J. de Vries, M. Takemura, S. Atarashi, and Philippus Elsinga
Subjects: Chemistry, medicine.drug_class, Organic Chemistry, Substituent, chemistry.chemical_element, Quinolone, Biochemistry, Analytical Chemistry, chemistry.chemical_compound, Drug Discovery, medicine, Fluorine, Organic chemistry, Radiology, Nuclear Medicine and imaging, Spectroscopy
Published: 2001
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39. Suitability of CGP-12177 and CGP-26505 for quantitative imaging of β-adrenoceptors

Author: Joan G. Meeder, Ki Lie, Philippus Elsinga, Anne M. J. Paans, Gerben M. Visser, van Aren Waarde, J. Bouwer, Pk Blanksma, W Vaalburg, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: Male, medicine.medical_specialty, DOWN-REGULATION, Time Factors, Quantitative imaging, RAT LUNG, Adrenergic receptor, ADRENERGIC-RECEPTOR, Metabolic Clearance Rate, Adrenergic beta-Antagonists, Tritium, SUBTYPES, Propanolamines, β adrenoceptor, NUMBER, In vivo, Internal medicine, Receptors, Adrenergic, beta, VENTRICULAR MYOCARDIUM, medicine, Animals, Tissue Distribution, Rats, Wistar, Lung, BETA-1-ADRENOCEPTOR, Chemistry, THYROID STATUS, Imidazoles, Antagonist, General Medicine, medicine.disease, Propranolol, Rats, Endocrinology, medicine.anatomical_structure, TISSUE, Heart failure, HEART-FAILURE, sense organs, Quantitative analysis (chemistry)
Abstract: [3H]CGP-12177, a non-selective beta-adrenoceptor antagonist, and [3H]CGP-26505, a beta 1-selective beta-adrenoceptor antagonist, were intravenously administered to rats. 94-97% of the injected radioactivity disappeared from plasma with t1/2 0.2 and 0.5 min. Total/non-specific binding ratios of 5.4 and 6.9 (CGP-12177) or 2.0 and 2.8 (CGP-26505) were maintained in heart and lung from 10 to 40 min post-injection. Labelled plasma metabolites appeared after greater than 20 min (CGP-12177) or within 2 min (CGP-26505). No metabolites were found in the heart. CGP-12177 binds to blood cells, but CGP-26505 does not. CGP-12177 can be used for PET imaging of total (beta 1 and beta 2) adrenoceptors in the heart and lung of experimental animals, but CGP-26505 is less suitable for in vivo analysis of the beta 1-subpopulation.
Published: 1992
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40. Some new cationic di‐ and tricarbonyl complexes of technetium(I)

Author: H. H. Knight Castro, W. Vaalburg, C. E. Hissink, K. Panek, and J.H. Teuben
Subjects: Stereochemistry, Cationic polymerization, chemistry.chemical_element, NOPF6, General Chemistry, TC-99M, Technetium, Medicinal chemistry, chemistry.chemical_compound, chemistry, RADIOACTIVITY, Acetonitrile, Isopropyl, AGENT
Abstract: Some new low-valent, cationic complexes of technetium-99 have been prepared. Oxidation of Tc2(CO)10 (1) with NOPF6 in acetonitrile gave [Tc(CH3CN)(CO)5]PF6 (2) quantitatively. This complex constitutes a useful precursor for cationic carbonyl complexes, as exemplified by a variety of reactions with bi- and tridentate ligands from which air-stable, water-soluble complexes of type [LTc(CO)3]+ (L = 1,4,7-triazacyclononane, 1,4,7-trimethyl-1,4,7-triazacyclononane and 1,4,7-trithiacyclononane) have been isolated and characterized. A series of mixed complexes of technetium(I) of general formula {Tc(N,N)[P(OR)3]2(CO)2}PF6 (N,N = 2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine and R = methyl, isopropyl) has also been prepared.
Published: 1992
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41. Preclinical evaluation of a positron emitting progestin ([18F]fluoro-16α-methyl-19-norprogesterone) for imaging progesterone receptor positive tumours with positron emission tomography

Author: G. Luurtsema, W Vaalburg, A. Verhagen, T.J. de Groot, J.W. Pesser, S. Wouda, and J.W. Oosterhuis
Subjects: Fluorine Radioisotopes, Cancer Research, medicine.medical_specialty, medicine.drug_class, Estrogen receptor, Biology, chemistry.chemical_compound, In vivo, Internal medicine, Progesterone receptor, medicine, Animals, Tissue Distribution, Receptor, Estrous cycle, Uterus, Mammary Neoplasms, Experimental, Rats, Inbred Strains, 19-Norprogesterone, Rats, Progesterone Receptor Positive, Endocrinology, Oncology, chemistry, Estrogen, Female, Receptors, Progesterone, Norprogesterones, Tomography, Emission-Computed
Abstract: Three 21-fluoro-progestins were investigated as potential imaging agents for the in vivo assessment of human progesterone receptor positive neoplasms with positron emission tomography. In competitive binding assays these compounds demonstrated high specificity, competing only for progesterone receptors. Binding to other steroid receptor types was negligible. Based on its high affinity binding, 21-fluoro-16α-methyl-19-norprogesterone was selected for further evaluation in vivo. Tissue distribution studies in immature estrogen primed female rats revealed high uterine uptake of 21-[18F]fluoro-16α-methyl-19-norprogesterone ([18F]FMNP). At 60 min after injection the ratio of uptake of radioactivity by uterine tissue to that of blood was 7. This ratio increased to 24 at 180 min. A selective decrease in uterine uptake was observed after administration of [18F]FMNP with excess unlabelled progestin. Rats bearing hormone responsive MT-W9A mammary adenocarcinomas were used to examine [18F]FMNP for tumour uptake. Animals were used irrespective of the phase of the estrous cycle. At 180 min the uterus to blood ratio and the tumour to blood ratio ranged from 3 to 20 and 3 to 17, respectively. Uterine and tumour tissue was assayed for cytosolic estrogen and progesterone receptors using a dextran-coated charcoal method and Scatchard plot analysis. The results indicate that the in vivo uptake of [18F]FMNP by uterine and mammary tumour tissue correlated well with the progesterone receptor concentration (rs = 0.98 and rs = 0.88, respectively). It is concluded that the uptake of [18F]FMNP by progesterone receptor positive tissue in vivo is primarily receptor related and that this uptake is attributable to the progesterone receptor. The study demonstrates the potential applicability of [18F]FMNP and positron emission tomography for imaging progesterone receptor positive neoplasms.
Published: 1991
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42. Synthesis, reactions and structure of Cp´Tc(CO)3 derivatives

Author: K. Panek, H. H. Knight Castro, Jan H. Teuben, G. Ensing, W. Vaalburg, and Auke Meetsma
Subjects: Stereochemistry, Organic Chemistry, Cationic polymerization, Crystal structure, Biochemistry, Medicinal chemistry, Inorganic Chemistry, chemistry.chemical_compound, Transition metal, Main group element, Cyclopentadienyl complex, chemistry, Yield (chemistry), Materials Chemistry, Physical and Theoretical Chemistry, Acetonitrile, Methyl iodide
Abstract: A novel procedure for a high yield synthesis of Tc 2 (CO) 10 is reported. Cyclopentadienyl technetium carbonyl complexes of general formula Cp′Tc(CO) 3 , where Cp′ = η 5 -C 5 H 5 , η 5 -C 5 Me 5 , or η 5 -C 5 (Me) 4 [(CH 2 ) 3 NMe 2 ], have been prepared by reaction of Tc(CO) 5 I with the appropriate lithium cyclopentadienide in THF at room temperature. Quaternization of the amino group in the cyclopentadienyl derivative 3 with methyl iodide is described and the results of an X-ray structure determination are presented. Treatment of (C 5 Me 5 )Tc(CO) 3 with NOPF 6 in acetonitrile affords the cationic nitrosyl [(C 5 Me 5 )Tc(CO) 2 (NO)][PF 6 ] in high yield, while treatment with Br 2 /CF 3 COOH gives the neutral dicarbonyl (C 5 Me 5 )Tc(CO) 2 Br 2 as a mixture of cis - and trans -isomers.
Published: 1991

43. Imaging of P glycoprotein Function in vivo with PET

Author: W. Vaalburg and N. H. Hendrikse
Subjects: Drug, Messenger RNA, endocrine system diseases, integumentary system, biology, Chemistry, media_common.quotation_subject, Cell, female genital diseases and pregnancy complications, Cell biology, carbohydrates (lipids), Cell membrane, medicine.anatomical_structure, In vivo, polycyclic compounds, medicine, biology.protein, Efflux, Function (biology), media_common, P-glycoprotein
Abstract: P glycoprotein (Pgp) is expressed on cell membranes of various organs in the body, such as the capillary endothelial cells of the brain. Furthermore, Pgp can also be expressed on the cell membrane of tumour cells. Because of Pgp-mediated efflux, tissue levels of several Pgp substrates are lower than in Pgp-negative tissues. Drug levels in Pgp-expressing organs may be increased by modulation of this Pgp-facilitated transport with several compounds, such as cyclosporin A. Up to now, the presence of drug efflux pumps in tissues could only be examined at the mRNA and protein level. However, this gives no insight into the important question of the functionality of these drug efflux pumps. Information about the transport function of Pgp and the effect of modulating this function may improve the therapeutic treatment of these patients. Positron emission tomography (PET) gives us a unique opportunity to study non-invasively (patho)physiological dynamic processes in vivo. We have therefore developed and validated a method for studying Pgp-mediated transport and its modulation in vivo with PET.
Published: 2008
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44. Ornithine decarboxylase activity in prostate and tumor: a feasibility study for PET with l-[1-14C]- and l-[5-14C]ornithine

Author: Bernard J. G. Daemen, W Vaalburg, Ph.H. Elsinga, and Kiichi Ishiwata
Subjects: chemistry.chemical_classification, medicine.medical_specialty, genetic structures, business.industry, fungi, General Medicine, Ornithine, Ornithine decarboxylase activity, In vitro, Ornithine decarboxylase, chemistry.chemical_compound, medicine.anatomical_structure, Enzyme, Endocrinology, chemistry, Prostate, Internal medicine, medicine, Distribution (pharmacology), Odc activity, business
Abstract: The aim of this study is to investigate the possibility of measuring ornithine decarboxylase (ODC) activity in tissues such as prostate and tumor, by PET. The ODC activity in vitro and the distribution of l-[1-14C]- and l-[5-14C]ornithine were studied in prostate, tumor, liver and kidney. For the animal models, rats bearing Walker 256 carcinosarcoma, were used. Our results indicate that the ODC activity in prostate is correlated with the difference in uptake between l-[1-14C]- and l-[5-14C]ornithine. Measurement of ODC activity in tumor by PET demands a tumor with an ODC activity comparable to that of prostate. Such a tumor will show a sufficient difference in uptake, which can be detected by PET.
Published: 1990
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45. An improved synthesis of carbon-11 labeled acetoacetic acid and an evaluation of its potential for the investigation of cerebral pathology by positron emission tomography

Author: W Vaalburg, G. H. M. Prenen, Anne M. J. Paans, K.G. Go, and F. Zuiderveen
Subjects: Male, High-performance liquid chromatography, Acetoacetates, Lesion, chemistry.chemical_compound, medicine, Acetone, Animals, Carbon Radioisotopes, Carbanion, Cerebral Cortex, CATS, medicine.diagnostic_test, business.industry, Radiochemistry, General Engineering, Rats, Inbred Strains, Rats, Acetoacetic acid, Carboxylation, chemistry, Positron emission tomography, Isotope Labeling, Cats, Female, medicine.symptom, Nuclear medicine, business, Tomography, Emission-Computed
Abstract: 1-11C-acetoacetic acid was synthesized by carboxylation of the acetone carbanion. Purification was carried out using HPLC. The product was obtained with a radiochemical yield of up to 58%, corrected for decay, in a total preparation time of 30 min. The distribution of 1-11C-acetoacetic acid after injection into adult Wistar rats and cats was investigated by PET. When the tracer was injected into cats, 3 weeks after inflicting a unilateral freezing lesion upon the brain, accumulation of 1-11C-acetoacetic acid in the ipsilateral brain hemisphere was observed.
Published: 1990
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46. Enzymatic synthesis of [4-methoxy-11C]daunorubicin for functional imaging of P-glycoprotein with PET

Author: Philippus Elsinga, W Vaalburg, E Eriks-Fluks, NH Hendrikse, Ejf Franssen, and Clinical pharmacology and pharmacy
Subjects: Stereochemistry, Daunorubicin, Methylation, chemistry.chemical_compound, medicine, ATP Binding Cassette Transporter, Subfamily B, Member 1, Carbon Radioisotopes, P-glycoprotein, chemistry.chemical_classification, Radiation, Methionine, biology, Carubicin, Total synthesis, Multiple drug resistance, Enzyme, chemistry, Biochemistry, Isotope Labeling, biology.protein, Radiopharmaceuticals, Tomography, Emission-Computed, Methyl iodide, medicine.drug
Abstract: One of the mechanisms for multidrug resistance (MDR) of tumors is an overexpression of the P-glycoprotein (P-gp). The cytostatic agent daunorubicin was labeled with carbon-11 to probe P-gp with PET. An enzymatic route for the conversion of carminomycin to [4-methoxy-11C]daunorubicin ([4-methoxy-11C]DNR) was investigated, since attempts failed to prepare daunorubicin chemically using [11C]methyl iodide. In the enzymatic synthesis methylation was accomplished by S-adenosyl-L-[methyl- 11C]methionine ([11]SAM), which was synthesized from L-[methyl- 11C]methionine. This methylation is catalyzed by carminomycin-4-O- methyltransferase (CMT). The overall radiochemical yield of [4- methoxy.11C]DNR is 1% (EOB), with a total synthesis time of 75 min. In conclusion, [4-methoxy-11C]DNR can be successfully prepared from carminomycin and [11C]SAM using enzymes.
Published: 1998
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47. Antagonism of HSV-tk transfection and ganciclovir treatment on chemotherapeutic drug sensitivity

Author: Gert Jan Meersma, W Vaalburg, L De Vries, E Kamstra, I J van Dillen, C. J. L. M. Meijer, van der Ate Zee, Nanno Mulder, de Elisabeth G. E. Vries, Wendy Dam, and Geesiena Hospers
Subjects: Ganciclovir, viruses, Genetic enhancement, medicine.medical_treatment, Antineoplastic Agents, Pharmacology, Biology, Transfection, Thymidylate synthase, Antiviral Agents, Thymidine Kinase, medicine, Tumor Cells, Cultured, Animals, Simplexvirus, Pharmacology (medical), Drug Interactions, Cisplatin, Chemotherapy, Brain Neoplasms, Genetic Therapy, Glioma, Rats, Infectious Diseases, Oncology, Thymidine kinase, Cancer research, biology.protein, Methotrexate, Drug Screening Assays, Antitumor, medicine.drug
Abstract: Our study focused on the influence of herpes simplex virus thymidine kinase (HSV-tk) expression and ganciclovir (GCV) treatment on the sensitivity of C6 glioma cells to frequently used chemotherapeutic drugs, i.e. adriamycin (ADR), cisplatin (CDDP), 5-fluorouracil (5-FU), and methotrexate (MTX). Transfection with HSV-tk revealed an increased sensitivity to GCV and CDDP and a decreased sensitivity to ADR and MTX. No significant differences were found in sensitivity to 5-FU. Combined treatment in a HSV-tk negative cell line revealed an additive effect when GCV was combined with ADR, whereas an antagonistic effect was found when GCV was combined with CDDP, 5-FU, or MTX. Comparable results were obtained in an HSV-tk positive cell line, apart from CDDP, which showed an additive effect. In conclusion, both HSV-tk transfection and subsequent GCV treatment can influence the sensitivity of tumor cells to various chemotherapeutic drugs in an antagonistic manner. Therefore, combining HSV-tk/GCV gene therapy with chemotherapy might not always be beneficial.
Published: 2005

48. Pulmonary Function Imaging with PET Radiopharmaceuticals

Author: W. Vaalburg and P.H. Elsinga
Subjects: medicine.medical_specialty, business.industry, Medicine, Radiology, business, Pulmonary function testing
Published: 2005
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49. In vivo uptake of [11C]choline does not correlate with cell proliferation in human prostate cancer

Author: W Vaalburg, Anthonius J. Breeuwsma, Igle J. de Jong, Maud M G J Jongen, Albert J. H. Suurmeijer, Rien J.M. Nijman, Jan Pruim, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: Oncology, Male, medicine.medical_specialty, CARCINOMA, medicine.medical_treatment, Statistics as Topic, METABOLISM, Choline, chemistry.chemical_compound, Prostate cancer, POSITRON-EMISSION-TOMOGRAPHY, Internal medicine, ANTIGEN RETRIEVAL, KI-67, medicine, Carcinoma, Tumor Cells, Cultured, Humans, Radiology, Nuclear Medicine and imaging, Carbon Radioisotopes, Aged, Cell Proliferation, medicine.diagnostic_test, biology, Cell growth, business.industry, Cancer, Prostatic Neoplasms, NUCLEAR ANTIGEN, General Medicine, Middle Aged, prostate cancer, medicine.disease, Radiation therapy, PET, chemistry, TISSUE, Positron emission tomography, Ki-67, Positron-Emission Tomography, biology.protein, DISTANT METASTASIS, Radiopharmaceuticals, business, RADIOTHERAPY
Abstract: Purpose: Prostate cancer is the second leading cause of death from cancer among US men. Positron emission tomography (PET) with [C-11] choline has been shown to be useful in the staging and detection of prostate cancer. The background of the increased uptake of choline in human prostate cancer is not completely understood. The aim of this study was to prospectively investigate the relationship between the [C-11] choline uptake and the cell proliferation in human prostate cancer.Methods: Prostate cancer tissue from 18 patients who had undergone a radical prostatectomy for histologically proven disease was studied. An [C-11] choline PET scan was performed prior to surgery. Post-prostatectomy specimens were prepared and stained with the antibody MIB-1 for Ki-67, which depicts proliferation. Two independent observers counted the amount of stained nuclei per specimen.Results: Prostate cancer showed Ki-67 staining and high uptake of [C-11] choline. Statistical analysis showed no significant correlation between [C-11] choline uptake and Ki-67 staining (R = 0.23; P = 0.34). No significant relationships were found between the uptake of [C-11] choline (SUV) and either preoperative PSA (R = 0.14; P = 0.55) or Gleason sum score (R = 0.28; P = 0.25).Conclusion: In vivo uptake of [C-11] choline does not correlate with cell proliferation in human prostate cancer as depicted by Ki-67. Our results suggest that a process other than proliferation is responsible for the uptake of [C-11] choline in prostate cancer.
Published: 2004

50. Detection and grading of soft tissue sarcomas of the extremities with (18)F-3'-fluoro-3'-deoxy-L-thymidine

Author: Philip H. Elsinga, Albert J. H. Suurmeijer, David Cobben, Bram Maas, W Vaalburg, Piet L. Jager, and Harald J. Hoekstra
Subjects: Male, Cancer Research, Fluorine Radioisotopes, Soft Tissue Neoplasm, Soft Tissue Neoplasms, medicine, Humans, Tissue Distribution, L-thymidine, Grading (education), Aged, medicine.diagnostic_test, business.industry, Soft tissue sarcoma, Soft tissue, Magnetic resonance imaging, Sarcoma, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Dideoxynucleosides, Oncology, Positron emission tomography, Female, Nuclear medicine, business, Tomography, Emission-Computed
Abstract: Purpose: The aim of the study was to investigate the feasibility of 18F-3′-fluoro-3′-deoxy-l-thymidine positron emission tomography (FLT-PET) for the detection and grading of soft tissue sarcoma (STS). Experimental Design: Nineteen patients with 20 STSs of the extremities were scanned, using attenuation corrected whole-body FLT-PET. Standardized uptake values (SUVs) and tumor:nontumor ratios (TNTs) were compared with histopathological parameters using French and Japanese grading systems. Results: Mean SUV, maximal SUV, and TNT could differentiate between low-grade (grade 1; n = 6) STS and high-grade (grade 2 and 3; n = 14) STS according to the French grading system (P = 0.001). Mean SUV, max SUV, and TNT correlated with mitotic score, MIB-1 score, the French and Japanese grading system (• = 0.550–0.747). Conclusions: FLT-PET is able to visualize STS and differentiate between low-grade and high-grade STS. The uptake of FLT correlates with the proliferation of STS.
Published: 2004

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