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

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Abstract
Background and Purpose: Non‐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 [18F]MA3, a CB2 receptor agonist, in a rat model with local overexpression of human (h) CB2 receptors.Methods: [18F]MA3 was produced with good radiochemical yield and radiochemical purity. The radiotracer was evaluated in rats with local overexpression of hCB2 receptors and in a healthy non‐human primate using PET.Key Results: Ex vivo autoradiography demonstrated CB2‐specific binding of [18F]MA3 in rat hCB2 receptor vector injected striatum. In a PET study, increased tracer binding in the hCB2 receptor vector‐injected striatum compared to the contralateral control vector‐injected striatum was observed. Binding in hCB2 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. [18F]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 Implications: Evaluation of [18F]MA3 in a rat model with local overexpression of hCB2 receptors showed CB2 receptor‐specific and reversible tracer binding. [18F]MA3 showed good brain uptake and subsequent washout in a healthy non‐human primate, but no specific binding was observed. Further clinical evaluation of [18F]MA3 in patients with neuroinflammation is warranted.Linked Articles: This article is part of a themed section on 8th 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
Funding Information
  • IMIR ( In vivo Molecular Imaging Research group), KU Leuven
  • FWO-Flanders (G0007.12)
  • INMiND (HEALTH-F2-2011-278850)
  • MIRIAD (130065)
  • IMIR (In Vivo Molecular Imaging Research group), KU Leuven

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