Distribution of cocaine recognition sites in monkey brain: II. Ex vivo autoradiography with [3H]CFT and [125I]RTI-55.

CFT [WIN 35,428, 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane] and its 4-iodinated analog RTI-55 have been proposed as imaging probes for cocaine recognition sites and for dopamine transporters. The central and peripheral distribution of radiolabeled forms of these compounds was studied 30 minutes after intravenous administration in squirrel monkey (Saimiri sciureus). Quantitative ex vivo autoradiography of brain tissue sections from animals receiving [3H]CFT (2.5 nmol/kg) revealed radioligand distribution primarily in dopamine-rich brain regions, and treatment with cocaine or mazindol substantially reduced [3H]CFT accumulation. The caudate nucleus, putamen, and nucleus accumbens/olfactory tubercle accumulated the highest levels of [3H]CFT, and within the caudate nucleus, medial-to-lateral and anterior-to-posterior gradients were observed. Low levels of [3H]CFT were found in the cortex, thalamus, hypothalamus, and background levels in white matter and in the cerebellum (striatal:cerebellar ratio > 3). The in vivo distribution of [3H]CFT closely paralleled its in vitro distribution (Synapse, 9:177-187). Although [125I]RTI-55 (0.2 nmol/kg) also distributed to dopamine-rich brain regions (striatal: cerebellar ratio of 3.6), high levels also were detected in cortex, thalamus, and in midbrain/brainstem structures. In the periphery, [125I]RTI-55 accumulation, measured as percent of administered dose, was higher than [3H]CFT in liver and lung, respectively. Of the radioactivity detected in soluble extracts of striatum, liver, and lung, greater than 90% comigrated with [3H]CFT or [125I]RTI-55 standards. The results support the hypothesis that dopamine-rich brain regions may be relevant to the effects of cocaine, and that both CFT and RTI-55 may be suitable imaging probes for these sites.