4 results on '"Janine Doorduin"'
Search Results
2. Evaluation of [C-11]-DAA1106 for imaging and quantification of neuro inflammation in a rat model of herpes encephalitis
- Author
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Hans C. Klein, Rudi Dierckx, Erik F. J. de Vries, Johan R. de Jong, Janine Doorduin, Molecular Neuroscience and Ageing Research (MOLAR), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
Male ,Cancer Research ,Biodistribution ,Pathology ,medicine.medical_specialty ,Positron emission tomography ,Herpesvirus 1, Human ,[C-11]-DAA1106 ,Central nervous system disease ,HIGH-AFFINITY ,POSITRON-EMISSION-TOMOGRAPHY ,Neuroinflammation ,In vivo ,Acetamides ,BINDING ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Tissue Distribution ,PERIPHERAL BENZODIAZEPINE-RECEPTOR ,Rats, Wistar ,BRAIN ,Inflammation ,medicine.diagnostic_test ,Microglia ,business.industry ,Phenyl Ethers ,Herpes viruses ,NEUROLOGICAL DISORDERS ,medicine.disease ,[C-11]-PK11195 ,DAA1106 ,Rats ,Disease Models, Animal ,medicine.anatomical_structure ,PET ,Positron-Emission Tomography ,Molecular Medicine ,Encephalitis, Herpes Simplex ,LIGAND ,business ,Encephalitis ,Ex vivo ,TSPO - Abstract
Many neurological and psychiatric disorders are associated with neuroinflammation. Positron emission tomography (PET) with [(11)C]-PK11195 can be used to study neuroinflammation in these disorders. However, [(11)C]-PK11195 may not be sensitive enough to visualize mild neuroinflammation. As a potentially more sensitive PET tracer for neuroinflammation, [(11)C]-N-(2,5-dimethoxybenzyl)-N-(4-fluoro-2-phenoxyphenyl)-acetamide (DAA1106) was evaluated in a rat model of herpes encephalitis.Male Wistar rats were intranasally inoculated with HSV-1 (HSE) or phosphate-buffered saline (control). At Day 6 or Day 7 after inoculation, small-animal [(11)C]-DAA1106 PET scans were acquired, followed by ex vivo biodistribution. Arterial blood sampling was performed for quantification of uptake.In HSE rats, a significantly higher ex vivo, but not in vivo, uptake of [(11)C]-DAA1106 was found in almost all examined brain areas (24-71%, P.05), when compared to control rats. Pretreatment with unlabeled PK11195 effectively reduced [(11)C]-DAA1106 uptake in HSE rats (54-84%; P.001). The plasma and brain time-activity curves showed rapid uptake of [(11)C]-DAA1106 into tissue. The data showed a good fit to the Logan analysis but could not be fitted to a two-tissue compartment model.[(11)C]-DAA1106 showed a high and specific ex vivo uptake in the encephalitic rat brain. However, neuroinflammation could not be demonstrated in vivo by [(11)C]-DAA1106 PET. Quantification of the uptake of [(11)C]-DAA1106 using plasma sampling is not optimal, due to rapid tissue uptake, slow tissue clearance and low plasma activity.
- Published
- 2010
3. Can celecoxib affect P-glycoprotein-mediated drug efflux? A microPET study
- Author
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Rudi Dierckx, Namkje A.R. Vellinga, Hans C. Klein, Janine Doorduin, Erik F. J. de Vries, Aren van Waarde, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Molecular Neuroscience and Ageing Research (MOLAR), and Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE)
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Male ,Cancer Research ,positron emission tomography ,Pharmacology ,nonsteroidal anti-inflammatory drug ,Radioligand Assay ,Cyclosporin a ,polycyclic compounds ,Tissue Distribution ,CYTOTOXICITY ,Carbon Radioisotopes ,MULTIDRUG-RESISTANCE ,P-glycoprotein ,Sulfonamides ,biology ,integumentary system ,celecoxib ,Brain ,medicine.anatomical_structure ,Molecular Medicine ,Efflux ,[C-11]verapamil ,medicine.drug ,Biological Transport, Active ,Blood–brain barrier ,Binding, Competitive ,In vivo ,CYCLOOXYGENASE-2 INHIBITOR ,medicine ,RISPERIDONE ,Animals ,Radiology, Nuclear Medicine and imaging ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Rats, Wistar ,MODULATION ,Brain Chemistry ,business.industry ,BLOOD-BRAIN-BARRIER ,IN-VITRO ,blood-brain barrier ,Rats ,PET ,Verapamil ,Positron-Emission Tomography ,biology.protein ,Celecoxib ,Pyrazoles ,CYCLOSPORINE ,Radiopharmaceuticals ,business ,COX-2 EXPRESSION ,Ex vivo - Abstract
Introduction: P-glycoprotein (Pgp) is an efflux pump that protects vital organs like the brain from toxic substances, but which is also associated with therapy resistance. The anti-inflammatory drug celecoxib potentiates the efficacy of several cytostatic and neurotropic drugs that are known Pgp substrates. To clarify whether Pgp is involved in the sensitizing effect of celecoxib, we investigated in vivo whether celecoxib is a substrate of Pgp and whether it can affect the efflux activity of the pump.Methods: In control rats and in rats treated with the Pgp modulator cyclosporin A (CsA), cerebral accumulation of radiolabeled [C-11] celecoxib was investigated by ex vivo biodistribution and micro-positron emission tomography imaging. In addition, the effect of unlabeled celecoxib and CsA (positive control) on the cerebral uptake of the Pgp substrate [C-11]verapamil was studied.Results: [C-11]Celecoxib uptake in rat brain was relatively high and homogeneously distributed. Treatment of rats with CsA only marginally increased cerebral tracer uptake, which is most likely due to reduced tracer clearance from plasma. [C-11]Verapamil brain uptake was more than 10-fold higher after treatment with CsA. In contrast, a high dose of celecoxib increased cerebral [C-11]verapamil uptake only twofold, which was accompanied by a similar increase in tracer concentration in plasma.Conclusions: This study shows that celecoxib is not a substrate of Pgp and does not substantially affect the Pgp-mediated efflux of [C-11] verapamil. Therefore, celecoxib-induced augmentation of the efficacy of chemotherapeutic and neurotropic drugs must be due to another mechanism than modulation of Pgp-mediated drug efflux. (C) 2008 Elsevier Inc. All rights reserved.
- Published
- 2008
4. In vivo imaging of brain androgen receptors in rats: a [(18)F]FDHT PET study
- Author
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Janine Doorduin, Inês Antunes, M. A. Khayum, Chantal Kwizera, J.A. den Boer, R. Zijlma, E. F. J. de Vries, Rudi Dierckx, Molecular Neuroscience and Ageing Research (MOLAR), Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)
- Subjects
EXPRESSION ,Male ,Cancer Research ,medicine.medical_specialty ,Biodistribution ,Positron emission tomography ,Fluorine Radioisotopes ,medicine.drug_class ,Neuroimaging ,Anterior pituitary ,Internal medicine ,TESTOSTERONE ,BINDING ,medicine ,Image Processing, Computer-Assisted ,Animals ,Radiology, Nuclear Medicine and imaging ,Tissue Distribution ,16β-[18F]fluoro-5α-dihydrotestosterone ([18F]FDHT) ,Rats, Wistar ,medicine.diagnostic_test ,Chemistry ,16 beta-[(18) F]fluoro-5 alpha-dihydrotestosterone ([F-18]FDHT) ,Brain ,MEN ,Dihydrotestosterone ,Androgen ,CANCER ,Rats ,Androgen receptor ,ANTERIOR-PITUITARY ,medicine.anatomical_structure ,Endocrinology ,Radiology Nuclear Medicine and imaging ,Receptors, Androgen ,Positron-Emission Tomography ,CELLS ,Molecular Medicine ,Radiopharmaceuticals ,3-BETA-HYDROXYSTEROID DEHYDROGENASE ,MESSENGER-RNA ,Preclinical imaging ,Ex vivo ,Small animal imaging ,medicine.drug - Abstract
INTRODUCTION: Steroid hormones like androgens play an important role in the development and maintenance of several brain functions. Androgens can act through androgen receptors (AR) in the brain. This study aims to demonstrate the feasibility of positron emission tomography (PET) with 16β-[(18)F]fluoro-5α-dihydrotestosterone ([(18)F]FDHT) to image AR expression in the brain.METHODS: Male Wistar rats were either orchiectomized to inhibit endogenous androgen production or underwent sham-surgery. Fifteen days after surgery, rats were subjected to a 90-min dynamic [(18)F]FDHT PET scan with arterial blood sampling. In a subset of orchiectomized rats, 1mg/kg dihydrotestosterone was co-injected with the tracer in order to saturate the AR. Plasma samples were analyzed for the presence of radioactive metabolites by radio-TLC. Pharmacokinetic modeling was performed to quantify brain kinetics of the tracer. After the PET scan, the animals were terminated for ex-vivo biodistribution.RESULTS: PET imaging and ex vivo biodistribution studies showed low [(18)F]FDHT uptake in all brain regions, except pituitary. [(18)F]FDHT uptake in the surrounding cranial bones was high and increased over time. [(18)F]FDHT was rapidly metabolized in rats. Metabolism was significantly faster in orchiectomized rats than in sham-orchiectomized rats. Quantitative analysis of PET data indicated substantial spill-over of activity from cranial bones into peripheral brain regions, which prevented further analysis of peripheral brain regions. Logan graphical analysis and kinetic modeling using 1- and 2-tissue compartment models showed reversible and homogenously distributed tracer uptake in central brain regions. [(18)F]FDHT uptake in the brain could not be blocked by endogenous androgens or administration of dihydrotestosterone.CONCLUSION: The results of this study indicate that imaging of AR availability in rat brain with [(18)F]FDHT PET is not feasible. The low AR expression in the brain, the rapid metabolism of [(18)F]FDHT in rats and the poor brain penetration of the tracer likely contributed to the poor performance of [(18)F]FDHT PET in this study.
- Published
- 2014
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