In vitro and ex vivo autoradiography studies on peripheral-type benzodiazepine receptor binding using [11C]AC-5216 in normal and kainic acid-lesioned rats

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 C-11. The aim of this study was to evaluate [C-11]AC-5216 in a rat brain model with neuroinflammation using an autoradiography (ARG) technique. In vitro ARG of normal rat brain showed that [C-11]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 [C-11]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 [C-11]AC-5216 and diminished the difference of radioactivity levels between the lesion and non-lesioned sides. These results demonstrated that [C-11]AC-5216 had high specific binding to PBR in the KA-lesioned rat brain. Thus, [C-11]AC-5216 is a promising PET ligand for imaging PBR in a brain with neuroinflammation. (C) 2007 Elsevier Ireland Ltd. All rights reserved.