title: In vitro and ex vivo autoradiography studies on peripheral-type benzodiazepine receptor binding using [11C]AC-5216 in normal and kainic acid-lesioned rats.
abstract: AC-5216 was reported as a novel ligand for peripheral-type benzodiazepine receptor (PBR) with a different chemical structure from DAA1106 analogues. This ligand had potent affinity for PBR and selectivity for PBR over other neurotransmitters. We have previously labeled AC-5216 using positron-emitter (11)C. The aim of this study was to evaluate [(11)C]AC-5216 in a rat brain model with neuroinflammation using an autoradiography (ARG) technique. In vitro ARG of normal rat brain showed that [(11)C]AC-5216 accumulated highly in the olfactory bulb, choroid plexus and cerebellum. The distribution pattern agreed with the localization of PBR in the rodent brain. Infusion of kainic acid (KA: 1, 2.5 and 5 nmol) into the rat striatum resulted in neuroinflammation. In vitro and ex vivo ARG revealed that the radioactivity level of [(11)C]AC-5216 was increased significantly in the KA-lesioned striatum compared to the non-lesioned striatum. Increasing the amount of KA infused into the striatum augmented radioactivity in the striatum as well as the cerebral cortex and hippocampus of the lesioned side. Treatment with a large amount of non-radioactive AC-5216 or PK11195 inhibited the binding of [(11)C]AC-5216 and diminished the difference of radioactivity levels between the lesion and non-lesioned sides. These results demonstrated that [(11)C]AC-5216 had high specific binding to PBR in the KA-lesioned rat brain. Thus, [(11)C]AC-5216 is a promising PET ligand for imaging PBR in a brain with neuroinflammation.
authors.affiliation: Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanamoto
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.forename: Katsushi
authors.initials: K
authors.lastname: Kumata
authors.forename: Akiko
authors.initials: A
authors.lastname: Hatori
authors.forename: Maki
authors.initials: M
authors.lastname: Okada
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007608:Kainic Acid; D008024:Ligands; D008297:Male; D009498:Neurotoxins; D049268:Positron-Emission Tomography / Q000379:methods; D011687:Purines / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D018690:Excitatory Amino Acid Agonists; D007546:Isoquinolines; D008024:Ligands; C502525:N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide; D009498:Neurotoxins; D011687:Purines; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; D007608:Kainic Acid; C037850:PK 11195