PET evaluation of [18F]FCWAY, an analog of the 5-HT1A receptor antagonist, WAY-100635

We synthesized [18F]FCWAY, an analog of [carbonyl-11C]WAY-100635 {[11C]N-(2-(1-(4-(2-methoxyphenyl)-piperazinyl)ethyl))-N-(2-(pyridinyl)) cyclohexanecarboxamide}, by replacing the cyclohexanecarbonyl group acid with a trans-4-fluorocyclohexane carbonyl group (FC). Control and preblocking studies were performed in anesthetized monkeys. Plasma radioactive metabolite analysis showed the presence of [18F]FC and [18F]fluoride. Tissue time-radioactivity curves were corrected for metabolite contamination based on separate positron-emission tomography studies of these two labeled metabolites. Analysis using a two-tissue compartment model gave distribution volume (V) estimates (mL/mL) ranging from 33 in frontal cortex to 4 in cerebellum. Preblocking data showed uniform V of 2-3 mL/mL. These studies demonstrate that [18F]FCWAY has very similar kinetic characteristics to [11C]WAY-100635.