Preclinical Evaluation Of [F-18]Ma3: A Cb2 Receptor Agonist Radiotracer For Pet

Background and PurposeNon-invasive in vivo imaging of cannabinoid CB2 receptors using PET is pursued to study neuroinflammation. The purpose of this study is to evaluate the in vivo binding specificity of [F-18]MA3, a CB2 receptor agonist, in a rat model with local overexpression of human (h) CB2 receptors.Methods[F-18]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 ResultsEx vivo autoradiography demonstrated CB2-specific binding of [F-18]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 CB2 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 CB2 receptor agonist PET tracers. [F-18]MA3 PET scans in the non-human primate showed good uptake and fast washout from brain, but no CB2 receptor-specific binding was observed.Conclusion and ImplicationsEvaluation of [F-18]MA3 in a rat model with local overexpression of hCB(2) receptors showed CB2 receptor-specific and reversible tracer binding. [F-18]MA3 showed good brain uptake and subsequent washout in a healthy non-human primate, but no specific binding was observed. Further clinical evaluation of [F-18]MA3 in patients with neuroinflammation is warranted.