[C-11] beta-CIT-FE, a radioligand for quantitation of the dopamine transporter in the living brain using positron emission tomography

The cocaine analogue beta-CIT-FE (N-(2-fluoroethyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane) was labeled with C-11 for positron emission tomography (PET) studies of the dopamine transporter. After intravenous administration to a cynomolgus monkey, [C-11]beta-CIT-FE accumulated in the striatum with a striatum-to-cerebellum ratio of about 9 after 60 min. Pseudoequilibrium of specific [C-11]beta-CIT-FE binding in the striatum was obtained within 30-50 min. The radioactivity ratios of the thalamus to the cerebellum and the neocortex to the cerebellum were about 2 and 1.5, respectively. In displacement and pretreatment experiments, radioactivity in the striatum but not in the cerebellum was reduced after injection of beta-CIT or the dopamine transporter inhibitor GBR 12909, indicating that striatal radioactivity following injection of [C-11]beta-CIT-FE represents reversible binding to dopamine transporter sites. After displacement or pretreatment with cocaine there was a marked effect not only in the striatum but also in the thalamus and neocortex. [C-11]beta-CIT-FE has potential as a useful PET radioligand for quantitation of the dopamine transporter in the primate brain in vivo. (C) 1996 Wiley-Liss, Inc.