title: Assessing the sensitivity of [¹¹C]p943, a novel 5-HT1B radioligand, to endogenous serotonin release.
abstract: The main objective of the current study was to determine the sensitivity of the positron emission tomography (PET) radioligand [¹¹C]P943 to fenfluramine-induced changes in endogenous 5-HT in nonhuman primate brain. Fenfluramine-induced changes in 5-HT(1B) occupancy were compared to those obtained by self-block with unlabeled P943. Two baboons and 1 rhesus monkey were given preblocking or displacing doses of fenfluramine (1-5 mg/kg) or preblocking doses of unlabeled P943 (0.2 mg/kg) and imaged with [¹¹C]P943 PET. Receptor occupancy by the low dose of fenfluramine (1 mg/kg) in the baboons was 25 and 29% and by the high dose of fenfluramine (5 mg/kg) in the rhesus macaque was 42%. Receptor occupancy by P943 (0.2 mg/kg) was 68 and 86% in the baboons. PET imaging of 5-HT(1B) receptors with [¹¹C]P943 may be a useful approach for measuring changes in endogenous 5-HT in the living human brain.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA. kelly.cosgrove@yale.edu
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Cosgrove
authors.forename: Tracy
authors.initials: T
authors.lastname: Kloczynski
authors.forename: Nabeel
authors.initials: N
authors.lastname: Nabulsi
authors.forename: David
authors.initials: D
authors.lastname: Weinzimmer
authors.forename: Shu-Fei
authors.initials: SF
authors.lastname: Lin
authors.forename: Julie K
authors.initials: JK
authors.lastname: Staley
authors.forename: Zubin
authors.initials: Z
authors.lastname: Bhagwagar
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D008024:Ligands; D048530:Papio anubis; D010879:Piperazines; D049268:Positron-Emission Tomography / Q000379:methods*; D011760:Pyrrolidinones; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D012680:Sensitivity and Specificity; D012701:Serotonin / Q000378:metabolism* / Q000502:physiology; D012702:Serotonin Antagonists
chemical_list: C546827:1-(4-(2-methoxyisopropyl)phenyl)-3-(2-(4-methylpiperazin-1-yl)benzyl)pyrrolidin-2-one; D002250:Carbon Radioisotopes; D008024:Ligands; D010879:Piperazines; D011760:Pyrrolidinones; D044302:Receptor, Serotonin, 5-HT1B; D012702:Serotonin Antagonists; D012701:Serotonin