Evaluation of cerebral cannabinoid type 2 receptors using [C]RSR-056 PET in a rat model of epilepsy.

Abstract

PURPOSE: Cannabinoid receptor type 2 (CB2R) plays a critical yet mechanistically undefined role in epileptogenesis. This study employed a CB2R-targeting PET probe to visualize spatiotemporal alterations in cerebral CB2R expression in epileptic rats, elucidating its potential role in epileptogenesis. METHODS: The CB2R-targeting PET probe [C]RSR-056 underwent automated radiosynthesis. A lithium chloride-pilocarpine-induced epileptic rat model was utilized, and [C]RSR-056 PET/CT imaging was performed in controls and status epilepticus (SE) groups (1 d, 1 w, 1&#x202f;m and 2&#x202f;m post SE). Image analysis using PMOD software yielded data expressed as standard uptake value (SUV) and the percentage of injected dose per gram of tissue (%ID/g). Immunofluorescence was performed on brain tissue from all groups. RESULTS: [C]RSR-056 PET/CT imaging revealed higher SUV in the hippocampus, thalamus, hypothalamus, and cerebellum of epileptic rats at 1 w post SE, and significantly higher %ID/g in the cortex, hippocampus, striatum, thalamus, hypothalamus, and cerebellum at both 1 d and 1 w post SE, compared with the control group (all P&#x202f;<&#x202f;0.05). Immunofluorescence confirmed CB2R co-localization in both microglia and neurons. Relative to controls, the 1 w post SE group showed a significant increase in the mean CB2R immunofluorescence intensity within the hippocampal CA1 region (P&#x202f;<&#x202f;0.05). CONCLUSION: CB2R-targeted PET probe [C]RSR-056 enables non-invasive visualization of spatiotemporal changes in brain CB2R expression of living epileptic rats. CB2R expression elevated at 1 d post SE, peaked at 1 w post SE, and declined to baseline at 1&#x202f;m and 2&#x202f;m post SE. Elevated CB2R expression was associated not only with microglia but also with neurons.