[C-11] WAY-100635 - A RADIOLIGAND FOR IMAGING 5-HT1A RECEPTORS WITH POSITRON EMISSION TOMOGRAPHY

The potent and selective 5-HT1A antagonist WAY 100635 azinyl]ethyl]-N- (2-pyridinyl)clohexanecarboxamide) was radiolabeled with C-11 in high specific activity, and the in vivo properties of this radioligand were assessed in the brains of rats and monkeys. Following i.v. tail vein injection in rats, [C-11]WAY 100635 rapidly penetrated into brain tiss ue and was retained over a 30-90 min time period in a manner consisten t with the known distribution of 5-HT1A receptors. Pretreatment of rat s with the selective 5-HT1A agonist (+/-)-8-OH-DPAT effectively blocke d the retention of radioactivity in brain regions known to contain hig h densities of 5-HT1A receptors. The hippocampus-to-cerebellum radioac tivity concentration ratio reached a maximum of 16:1 at 60 min post in jection. Following i.v. injection of [C-11]WAY 100635 in rhesus monkey s, the concentrations of radioactivity in brain regions were consisten t with the reported distribution of 5-HT1A receptors in primates, and the frontal cortex-to-cerebellum ratio reached 5.5:1 at 80 min post in jection. Pretreatment of the monkeys with (+/-)-8-OH-DPAT reduced this ratio to 1.4:1, and injection of (+/-)-8-OH-DPAT 20 min after the inj ection of [C-11]WAY100635 significantly displaced frontal cortex bindi ng. The in vivo properties of [C-11]WAY 100635 in rats and monkeys str ongly support the future utility of this radioligand for imaging 5-HT1 A receptors using positron emission tomography (PET).