IMAGING OF CHOLINERGIC TERMINALS USING THE RADIOTRACER [F-18] (-4-FLUOROBENZYLTROZAMICOL - IN-VITRO BINDING-STUDIES AND POSITRON EMISSION TOMOGRAPHY STUDIES IN NONHUMAN-PRIMATES())

The goal of the present set of studies was to characterize the in vitr o binding properties and in vivo tissue kinetics for the vesicular ace tylcholine transporter (VAcChT) radiotracer, [F-18](+)-4-fluorobenzylt rozamicol ([F-18](+)-FBT). In vitro binding studies were conducted in order to determine the affinity of the (+)- and (-)-stereoisomers of F BT for the VAcChT as well as sigma (sigma(1) and sigma(2)) receptors. (+)-FBT was found to have a high affinity (K-i = 0.22 nM) for the VAcC hT and lower affinities for sigma(1) (21.6 nM) and sigma(2) (35.9 nM) receptors, whereas (-)-FBT had similar affinities for the VAcChT and s igma(1) receptors (similar to 20 nM) and a lower affinity for sigma(2) (110 nM) receptors. PET imaging studies were conducted in rhesus monk eys (n = 3) with [F-18](+)-FBT. [F-18](+)-FBT was found to have a high accumulation and slow rate of washout from the basal ganglia, which i s consistent with the labeling of cholinergic interneurons in this bra in region. [F-18](+)-FBT also displayed reversible binding kinetics du ring the 3 h time course of PET and produced radiolabeled metabolites that did not cross the blood-brain barrier. The results from the curre nt in vitro and in vivo studies indicate that [F-18](+)-FBT is a promi sing ligand for studying cholinergic terminal density, with PET, via t he VAcChT. (C) 1997 Wiley-Liss, Inc.