摘要：The suitability of an 18F-labeled form of N -(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-{4′-(5-fluoropentyl)phenyl}-4-methyl-1 H -pyrazole-3-carboxamide (1), a CB1 cannabinoid ligand with high binding affinity ( K i=0.91 n M ) and moderate lipophilicity (log P 7.4=2.9), as a radiotracer for positron emission tomography imaging was evaluated in mice. Ligand 1 was labeled with 18F ( T 1/2=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 .
