[C-11] RO 15-4513, A LIGAND FOR VISUALIZATION OF BENZODIAZEPINE RECEPTOR-BINDING - PREPARATION, AUTORADIOGRAPHY AND POSITRON EMISSION TOMOGRAPHY

Ro 15-4513, a partial inverse agonist at the benzodiazepine (BZ) receptor site was labelled with C-11 and used for in vitro autoradiography on human post mortem brain sections and for positron emission tomography (PET) on Cynomolgus monkeys. The total radiochemical yield of [C-11]Ro 15-4513 was 30-40% with an overall synthesis time of 40 min. The specific radioactivity was about 1000 Ci/mmol at end of synthesis. In vitro autoradiography showed that [C-11]Ro 15-4513 bound specifically predominately in the neocortex of the human brain. Specific binding was also demonstrated in the basal ganglia and the cerebellar cortex. Flumazenil (Ro 15-1788) and clonazepam inhibited the binding in cerebral regions, but a significant proportion in the cerebellum was not inhibited by these agents. This proportion may represent alpha(6)-containing BZ receptors. PET examination of [C-11]Ro 15-4513 binding in Cynomolgus monkeys demonstrated high uptake of radioactivity in neocortex. The uptake of radioactivity was markedly displaced by high doses of Ro 15-4513 or clonazepam. [C-11]Ro 15-4513 should be a useful ligand to examine BZ receptor characteristics in the living human brain by PET.