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The cannabinoid type 2 (CB2) receptor has emerged as a valuable target for therapy and imaging of immune-mediated pathologies. With the aim to find a suitable radiofluorinated analogue of the previously reported CB2 positron emission tomography (PET) radioligand [¹¹C]RSR-056, 38 fluorinated derivatives were synthesized and tested by in vitro binding assays. With a K_i (hCB2) of 6 nM and a selectivity factor of nearly 700 over cannabinoid type 1 receptors, target compound 3 exhibited optimal in vitro properties and was selected for evaluation as a PET radioligand. [¹⁸F]3 was obtained in an average radiochemical yield of 11 ± 4% and molar activities between 33 and 114 GBq/μmol. Specific binding of [¹⁸F]3 to CB2 was demonstrated by in vitro autoradiography and in vivo PET experiments using the CB2 ligand GW-405 833. Metabolite analysis revealed only intact [¹⁸F]3 in the rat brain. [¹⁸F]3 detected CB2 …