Radiosynthesis and biodistribution in mice of a 18F-labeled analog of O-1302 for use in cerebral CB1 cannabinoid receptor imaging

Abstract

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 (K i=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. © 2008 Pharmaceutical Society of Japan.