[11C]Ro 15-4513, a ligand for visualization of benzodiazepine receptor binding |
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Authors: | Christer Halldin Lars Farde Jan-Eric Litton Håkan Hall Göran Sedvall |
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Affiliation: | (1) Department of Psychiatry and Psychology, Karolinska Hospital, S-10401 Stockholm, Sweden |
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Abstract: | Ro 15-4513, a partial inverse agonist at the benzodiazepine (BZ) receptor site was labelled with11C 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 [11C]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 [11C]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 6-containing BZ receptors. PET examination of [11C]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. [11C]Ro 15-4513 should be a useful ligand to examine BZ receptor characteristics in the living human brain by PET. |
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Keywords: | Benzodiazepine receptors Ro 15-4513 11C Positron emission tomography PET In vitro autoradiography Monkey brain Human brain |
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