EXQUISITE DELINEATION OF 5-HT1A RECEPTORS IN HUMAN BRAIN WITH PET AND[CARBONYL-C-11]WAY-100635

The 5-HT1A receptor antagonist, WAY-100635 -methoxyphenyl)-1-piperazin yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide], was labelled in its c arbonyl group with carbon-11 (t(1/2) = 20.4 min), injected intravenous ly into healthy male volunteers and studied with positron emission tom ography (PET). The acquired data provide exquisite delineation of 5-HT 1A receptors in brain, with the ratio of radioactivity uptake in recep tor-rich regions, such as medial temporal cortex, to that in receptor- devoid cerebellum reaching 25 by 60 min after radioligand injection. A pplication of biomathematical modelling to the data revealed high valu es (7.8) for binding potential, a measure of B-max/K-D, in receptor-ri ch regions. Only very polar radioactive metabolites were present in pl asma, a finding consistent with the low level of nonspecific binding s een in cerebellum. [carbonyl-C-11]WAY-100635 is concluded to be far su perior to the previously reported [O-methyl-C-11]WAY-100635 as a radio ligand for PET studies of 5-HT1A receptors in human brain.