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