Synthesis and preclinical evaluation of [11C]MA-PB-1 for in vivo imaging of brain monoacylglycerol lipase (MAGL)

Abstract MAGL is a potential therapeutic target for oncological and psychiatric diseases. Our objective was to develop a PET tracer for in vivo quantification of MAGL. We report [ 11 C]MA-PB-1 as an irreversible MAGL inhibitor PET tracer. The in vitro inhibitory activity, ex vivo distribution, brain kinetics and specificity of [ 11 C]MA-PB-1 binding were studied. Ex vivo biodistribution and microPET showed good brain uptake which could be blocked by pretreatment with both MA-PB-1 and a structurally non-related MAGL inhibitor MJN110. These initial results suggest that [ 11 C]MA-PB-1 is a suitable tracer for in vivo imaging of MAGL.