摘要Monoacylglycerol lipase(MAGL)constitutes a crucial serine hydrolase within the endocan-nabinoid system,which has been suggested as a potential therapeutic target for the treatment of various neurodegenerative disorders.While MAGL inhibitors have entered the clinical arena,a highly selective and MAGL-specific positron emission tomography(PET)ligand holds promise to significantly facilitate clinical drug development by allowing the quantification of MAGL levels and the assessment of target occupancy in patients.Accordingly,this study aimed to develop a new series of reversible MAGL inhib-itor candidates,based on a piperazinyl azetidine diamide scaffold.Compound 3 demonstrated the most promising performance characteristics in pharmacological evaluations compared to other MAGL inhib-itor candidates.Subsequently,it was labeled with fluorine-18 and further assessed through autoradiog-raphy and PET imaging,as well as ex vivo biodistribution and metabolite analysis experiments in rodents.Compound 3 exhibited a heterogeneous radioactivity distribution,favorable brain uptake,and excellent in vivo binding specificity.Target occupancy studies with a therapeutic MAGL inhibitor demon-strated a dose-dependent PET signal reduction of[18F]3 in rat brains.In conclusion,[18F]3([18F]MAGL-2011)has the potential to serve as an effective MAGL PET ligand.