Preclinical evaluation of [ 18 F]MA3: a CB 2 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 hCB 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 hCB 2 receptor vector injected striatum. In a PET study, increased tracer binding in the hCB 2 receptor vector-injected striatum compared to the contralateral control vector-injected striatum was observed. Binding in hCB 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 hCB 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.