Preclinical evaluation of [¹⁸F]MA3: a CB₂ receptor agonist radiotracer for PET

Abstract

Background and Purpose Non‐invasive in vivo imaging of cannabinoid CB 2 receptors using PET is pursued to study neuroinflammation. The purpose of this study is to evaluate the in vivo binding specificity of [ 18 F]MA3, a CB 2 receptor agonist, in a rat model with local overexpression of human ( h ) CB 2 receptors. Methods [ 18 F]MA3 was produced with good radiochemical yield and radiochemical purity. The radiotracer was evaluated in rats with local overexpression of h CB 2 receptors and in a healthy non‐human primate using PET. Key Results Ex vivo autoradiography demonstrated CB 2 ‐specific binding of [ 18 F]MA3 in rat h CB 2 receptor vector injected striatum. In a PET study, increased tracer binding in the h CB 2 receptor vector‐injected striatum compared to the contralateral control vector‐injected striatum was observed. Binding in h CB 2 receptor vector‐injected striatum was blocked with a structurally non‐related CB 2 receptor inverse agonist, and a displacement study confirmed the reversibility of tracer binding. This study identified the utility of mutated inactive vector model for evaluation of CB 2 receptor agonist PET tracers. [ 18 F]MA3 PET scans in the non‐human primate showed good uptake and fast washout from brain, but no CB 2 receptor‐specific binding was observed. Conclusion and Implications Evaluation of [ 18 F]MA3 in a rat model with local overexpression of h CB 2 receptors showed CB 2 receptor‐specific and reversible tracer binding. [ 18 F]MA3 showed good brain uptake and subsequent washout in a healthy non‐human primate, but no specific binding was observed. Further clinical evaluation of [ 18 F]MA3 in patients with neuroinflammation is warranted. Linked Articles This article is part of a themed section on 8 th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc