Abstract
Peripheral benzodiazepine receptors (PBRs) are upregulated on activated microglia. We recently developed a promising positron emission tomography (PET) ligand, [ 11C]PBR28, with high affinity and excellent ratio of specific to nonspecific binding. We assessed the ability of [ 11C]PBR28 PET to localize PBRs in a rat permanent middle cerebral artery occlusion (MCAO) model of neuroinflammation. [ 11C]PBR28 was intravenously administered to rats at 4 and 7 days after permanent MCAO. In all experiments, arterial blood was sampled for compartmental modeling of regional distribution volumes, and rat brains were sampled after imaging for in vitro [ 3H]PK 11195 autoradiography and histological evaluation. [ 11C]PBR28 PET and [ 3H]PK 11195 autoradiography showed similar areas of increased PBRs, especially in the peri-ischemic core. Results from these in vivo and in vitro methods were strongly correlated. In this first study to demonstrate neuroinflammation in vivo with small animal PET, [ 11C]PBR28 had adequate sensitivity to localize and quantify the associated increase in PBRs.
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