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Imaging of cholinergic terminals using the radiotracer [ 18 F](+)‐4‐fluorobenzyltrozamicol: In vitro binding studies and positron emission tomography studies in nonhuman primates
Author(s) -
Mach Robert H.,
Voytko Mary Lou,
Ehrenkaufer Richard L.E.,
Nader Michael A.,
Tobin Joseph R.,
Efange Simon M.N.,
Parsons Stanley M.,
Gage H. Donald,
Smith Cynthia R.,
Morton Thomas E.
Publication year - 1997
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/(sici)1098-2396(199704)25:4<368::aid-syn8>3.0.co;2-8
Subject(s) - cholinergic , in vivo , in vitro , chemistry , receptor , ligand (biochemistry) , kinetics , receptor–ligand kinetics , affinities , positron emission tomography , biophysics , biochemistry , neuroscience , biology , physics , microbiology and biotechnology , quantum mechanics
Abstract The goal of the present set of studies was to characterize the in vitro binding properties and in vivo tissue kinetics for the vesicular acetylcholine transporter (VAcChT) radiotracer, [ 18 F](+)‐4‐fluorobenzyltrozamicol ([ 18 F](+)‐FBT). In vitro binding studies were conducted in order to determine the affinity of the (+)‐ and (−)‐ stereoisomers of FBT for the VAcChT as well as sigma (σ 2 and σ 2 ) receptors. (+)‐FBT was found to have a high affinity (K i = 0.22 nM) for the VAcChT and lower affinities for σ 1 (21.6 nM) and σ 2 (35.9 nM) receptors, whereas (−)‐FBT had similar affinities for the VAcChT and σ 1 receptors (∼20 nM) and a lower affinity for σ 2 (110 nM) receptors. PET imaging studies were conducted in rhesus monkeys (n = 3) with [ 18 F](+)‐FBT. [ 18 F](+)‐FBT was found to have a high accumulation and slow rate of washout from the basal ganglia, which is consistent with the labeling of cholinergic interneurons in this brain region. [ 18 F](+)‐FBT also displayed reversible binding kinetics during the 3 h time course of PET and produced radiolabeled metabolites that did not cross the blood‐brain barrier. The results from the current in vitro and in vivo studies indicate that [ 18 F](+)‐FBT is a promising ligand for studying cholinergic terminal density, with PET, via the VAcChT. Synapse 25:368–380, 1997. © 1997 Wiley‐Liss, Inc.