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Assessing the sensitivity of [ 11 C]p943, a novel 5‐HT IB radioligand, to endogenous serotonin release
Author(s) -
Cosgrove Kelly P.,
Kloczynski Tracy,
Nabulsi Nabeel,
Weinzimmer David,
Lin ShuFei,
Staley Julie K.,
Bhagwagar Zubin,
Carson Richard E.
Publication year - 2011
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20942
Subject(s) - fenfluramine , radioligand , endogeny , serotonin , 5 ht receptor , receptor , medicine , positron emission tomography , pharmacology , endocrinology , chemistry , biology , neuroscience
The main objective of the current study was to determine the sensitivity of the positron emission tomography (PET) radioligand [ 11 C]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 [ 11 C]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 [ 11 C]P943 may be a useful approach for measuring changes in endogenous 5‐HT in the living human brain. Synapse, 2011. © 2011 Wiley‐Liss, Inc.