[F-18]beta-CIT-FP is superior to [C-11]beta-CIT-FP for quantitation of the dopamine transporter

beta-CIT-FP [N-(3-fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane] is a cocaine analogue with high affinity for the dopamine transporter. Positron emission tomography (PET) studies with [O-methyl-C-11]beta-CIT-FP ([C-11]beta-CIT-FP) has shown that equilibrium conditions were approached but, however, not reached at the end of measurement. Moreover, metabolite studies of [C-11]beta-CIT-FP in monkey plasma demonstrated a lipophilic-labelled metabolite that may enter the brain. We therefore labelled beta-CIT-FP with fluorine 18 in a position that may avoid the formation of labelled lipophilic metabolites. The more long-lived radionuclide (F-18) was used to allow for measurements over longer time. [N-fluoropropyl-F-18]beta-CIT-FP ([F-18]beta-CIT-FP) was prepared by N-alkylation of nor-beta-CIT with [F-18]fluoropropyl bromide. PET studies were performed in cynomolgus monkeys. [F-18]beta-CIT-FP entered the brain rapidly. There was a high concentration of radioactivity in the striatum and much lower in the thalamus, neocortex, and cerebellum. The striatum to-cerebellum ratio was about 5 at time of transient equilibrium, which occurred after 60 to 100 min. After pretreatment with GBR 12909, radioactivity in the striatum was markedly reduced, thus indicating specific [F-18]beta-CIT-FP binding to the dopamine transporter. The fraction of unchanged [F-18]beta-CIT-FP determined by HPLC was 10-15% after 140 min. No lipophilic labelled metabolites were detected. The absence of measurable lipophilic labelled metabolites and the occurrence of transient equilibrium within the time of the PET measurement indicate that [F-18]beta-CIT-FP is superior to [C-11]beta-CIT-FP as a PET radioligand for quantification of the dopamine transporter in the human brain, (C) 1997 Elsevier Science Inc.