Imaging of cholinergic terminals using the radiotracer [18F](+)-4-fluorobenzyltrozamicol: In vitro binding studies and positron emission tomography studies in nonhuman primates

✍ Scribed by Robert H. Mach; Mary Lou Voytko; Richard L.E. Ehrenkaufer; Michael A. Nader; Joseph R. Tobin; Simon M.N. Efange; Stanley M. Parsons; H. Donald Gage; Cynthia R. Smith; Thomas E. Morton

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 144 KB
• Volume: 25
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(199704)25:4<368::aid-syn8>3.0.co;2-8

✦ Synopsis

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 (1)-and (2)stereoisomers of FBT for the VAcChT as well as sigma (s 1 and s 2 ) receptors. (1)-FBT was found to have a high affinity (K i 5 0.22 nM) for the VAcChT and lower affinities for s 1 (21.6 nM) and s 2 (35.9 nM) receptors, whereas (2)-FBT had similar affinities for the VAcChT and s 1 receptors (,20 nM) and a lower affinity for s 2 (110 nM) receptors. PET imaging studies were conducted in rhesus monkeys (n 5 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.