Radiosynthesis and biodistribution in mice of a 18F-labeled analog of O-1302 for use in cerebral CB1 cannabinoid receptor imaging
| Autor: | Takahiro Mukai, Toru Sasada, Shintaro Tobiishi, Yumiko Nojiri, Minoru Maeda, Qinggeletu, Fumihiko Yamamoto, Kiichi Ishiwata |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Biodistribution Fluorine Radioisotopes Cannabinoid receptor medicine.medical_treatment Pharmaceutical Science Pharmacology Mice Piperidines Receptor Cannabinoid CB1 In vivo Cyclosporin a Radioligand medicine Animals Tissue Distribution Radionuclide Imaging Biotransformation Chemistry Radiosynthesis Brain General Medicine Ligand (biochemistry) Isotope Labeling Injections Intravenous Cyclosporine Pyrazoles Indicators and Reagents Cannabinoid Chromatography Thin Layer Radiopharmaceuticals Immunosuppressive Agents |
| Zdroj: | Biologicalpharmaceutical bulletin. 31(6) |
| ISSN: | 0918-6158 |
| Popis: | The suitability of an 18F-labeled form of N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4'-(5-fluoropentyl)phenyl)-4-methyl-1H-pyrazole-3-carboxamide (1), a CB1 cannabinoid ligand with high binding affinity (Ki=0.91 nM) and moderate lipophilicity (log P7.4=2.9), as a radiotracer for positron emission tomography imaging was evaluated in mice. Ligand 1 was labeled with 18F (T1/2=109.7 min) by treatment of the corresponding tosyl derivative with [18F]fluoride ion in acetonitrile. Tissue distribution studies of the 18F-labeled form ([18F]1) in mice demonstrated low brain uptake with minimal specific binding in brain regions. Cyclosporin A (a modulator of P-glycoprotein) treatment significantly increased both the brain uptake and the brain-to-blood ratio of [18F]1, indicating the possibility that P-glycoprotein regulates the ability of [18F]1 to cross the blood brain barrier. Radioligand [18F]1 does not have the required properties for imaging the cerebral cannabinoid CB1 receptor in vivo. |
| Databáze: | OpenAIRE |
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