Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-C-11]WAY-100635

The 5-HT1A receptor antagonist, WAY-100635 [N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide], was labelled in its carbonyl group with carbon-11 (t(1/2) = 20.4 min), injected intravenously into healthy male volunteers and studied with positron emission tomography (PET). The acquired data provide exquisite delineation of 5-HT1A receptors in brain, with the ratio of radioactivity uptake in receptor-rich regions, such as medial temporal cortex, to that in receptor-devoid cerebellum reaching 25 by 60 min after radioligand injection. Application of biomathematical modelling to the data revealed high values (7.8) for binding potential, a measure of B-max/K-D, in receptor-rich regions. Only very polar radioactive metabolites were present in plasma, a finding consistent with the low level of nonspecific binding seen in cerebellum. [carbonyl-C-11]WAY-100635 is concluded to be far superior to the previously reported [O-methyl-C-11]WAY-100635 as a radioligand for PET studies of 5-HT1A receptors in human brain.