title: Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-11 C]WAY-100635.
abstract: 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 (t1/2 = 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 Bmax/Kp, 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-11C]WAY-100635 is concluded to be far superior to the previously reported [0-methyl-11C]WAY-100635 as a radioligand for PET studies of 5-HT1A receptors in human brain.
authors.affiliation: MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK. vpike@rpms.ac.uk
authors.forename: V W
authors.initials: VW
authors.lastname: Pike
authors.forename: J A
authors.initials: JA
authors.lastname: McCarron
authors.forename: A A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: S
authors.initials: S
authors.lastname: Osman
authors.forename: S P
authors.initials: SP
authors.lastname: Hume
authors.forename: P A
authors.initials: PA
authors.lastname: Sargent
authors.forename: C J
authors.initials: CJ
authors.lastname: Bench
authors.forename: I A
authors.initials: IA
authors.lastname: Cliffe
authors.forename: A
authors.initials: A
authors.lastname: Fletcher
authors.forename: P M
authors.initials: PM
authors.lastname: Grasby
mesh_terms: D000328:Adult; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002250:Carbon Radioisotopes; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D010879:Piperazines / Q000493:pharmacokinetics; D011725:Pyridines / Q000493:pharmacokinetics; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide