A Novel Radiotracer for Imaging Monoacylglycerol Lipase in the Brain Using Positron Emission Tomography

Monoacylglycerol lipase (MAGL) is a serine hydrolase that hydrolyzes monoacylglycerols to glycerol and fatty acid and plays an important role in neuroinflammation. MAGL inhibitors are a class of molecules with therapeutic potential for human diseases of the central nervous system (CNS), in areas such as pain and inflammation, immunological disorders, and neurological and psychiatric conditions. Development of a noninvasive imaging probe would elucidate the distribution and functional roles of MAGL in the brain and accelerate medical research and drug discovery in this domain. Herein, we describe the synthesis and pilot rodent imaging of a novel MAGL imaging agent, [C-11]SAR127303. Our imaging results demonstrate the high specificity, good selectivity, and appropriate kinetics and distribution of [C-11]SAR127303, validating its utility for imaging MAGL in the brain. Our findings support the translational potential for human CNS MAGL imaging.