[C-11] BETA-CIT, A COCAINE ANALOG - PREPARATION, AUTORADIOGRAPHY AND PRELIMINARY PET INVESTIGATIONS

Beta-CIT (2beta-carbomethoxy-3beta-(4-iodophenyl)tropane) is a cocaine analogue with a high affinity for the dopamine transporter. [C-11]beta-CIT was prepared by N-methylation of nor-beta-CIT with [C-11]methyl iodide. The total radiochemical yield of [C-11]beta-CIT was 40-50% with an overall synthesis time of 35-40 min. The radiochemical purity was >99% and the specific radioactivity at the time of injection was about 1000 Ci/mmol (37 GBq/mumol). Autoradiographic examination of [C-11]beta-CIT binding in human brains post-mortem demonstrated a high level of specific binding in the striatum. PET examination of [C-11]beta-CIT in a Cynomolgus monkey showed a marked accumulation of radioactivity in the striatum. The ratio of radioactivity in the striatum-to-cerebellum approached 5 after 87 min. In a displacement experiment, radioactivity in the striatum but not in the cerebellum, was markedly reduced after injection of unlabelled cocaine. [C-11]beta-CIT has a potential as ligand for PET examination of cocaine effects in man.