Imaging 5-HT1A receptors with positron emission tomography:: Initial human studies with [11C]CPC-222

The novel radioligand [C-11]CPC-222 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)-2-bicyclo[2,2,2] octane carboxamide) was evaluated as an in vivo probe of the 5-HT1A receptors using positron emission tomography (PET). Three human volunteers were imaged with PET over a 90 min period following intravenous injection of the radioligand. There was a high accumulation of the radioligand in brain regions with a high density of 5-HT1A receptors. The peak cortical concentration was 1.0-2.5% of the injected dose per litre. The ratio of radioactivity in receptor-rich regions to that of the cerebellum reached a plateau of 2.5-4.0 by 45 min after injection. Analysis of the plasma revealed no detectable amount of the potential metabolite, radiolabelled WAY-100634. This new radioligand has suitable properties to study the 5-HT1A receptors in man with PET.