PET STUDY OF [C-11] BETA-CIT BINDING TO MONOAMINE TRANSPORTERS IN THEMONKEY AND HUMAN BRAIN

The cocaine congener beta-CIT has been labeled with C-11 for positron emission tomographic (PET) studies of the dopamine transporter. In the present autoradiographic study on human brain sections and PET study on monkey and human [C-11]beta-CIT accumulated markedly in the striatu m. [C-11]beta-CIT binding in the striatum was selective to the dopamin e transporter. The binding in the thalamus was on an intermediate leve l and was displaced by compounds having affinity for norepinephrine an d serotonin transporters. The neocortical binding was on a low level a nd could be displaced only by citalopram, a serotonin uptake inhibitor . A high dose of cocaine intravenously (7 mg/kg) induced a 50% occupan cy of specific [C-11]beta-CIT binding to the dopamine transporter in t he striatum. This dose is much higher than the doses of 0.25-0.5 mg/kg i.v. for cocaine arousal in human subjects. The finding indicates tha t cocaine arousal may be induced at a low dopamine transporter occupan cy of a few percent. [C-11]beta-CIT should be a useful radioligand to explore cocaine actions in humans and to follow the pathophysiological process in vivo by PET in neurodegenerative diseases of the striatum.