Elsevier

Neuroscience Letters

Volume 411, Issue 3, 16 January 2007, Pages 200-205
Neuroscience Letters

PET imaging with [11C]PBR28 can localize and quantify upregulated peripheral benzodiazepine receptors associated with cerebral ischemia in rat

https://doi.org/10.1016/j.neulet.2006.09.093Get rights and content

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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Acknowledgements

We thank John M. Hallenbeck for histological evaluation; Michael Green and Jurgen Seidel who built the rodent PET camera; Jeih-San Liow for processing PET data; and PMOD group for providing PMOD 2.65. This research was supported by the Intramural Program of NIMH (Project #Z01-MH-002795-04).

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