摘要Monoacylglycerol lipase(MAGL)constitutes a serine hydrolase that orchestrates endocannabinoid homeostasis and exerts its function by catalyzing the degradation of 2-arachidonoylglycerol(2-AG)to arachidonic acid(AA).As such,selective inhibition of MAGL represents a potential therapeutic and diagnostic approach to various pathologies including neurodegenerative disorders,metabolic diseases and cancers.Based on a unique 4-piperidinyl azetidine diamide scaffold,we developed a reversible and peripheral-specific radiofluorinated MAGL PET ligand[18F]FEPAD.Pharmacokinetics and binding studies on[18F]FEPAD revealed its outstanding specificity and selectivity towards MAGL in brown adipose tissue(BAT)-a tissue that is known to be metabolically active.We employed[18F]FEPAD in PET studies to assess the abundancy of MAGL in BAT deposits of mice and found a remarkable degree of specific tracer binding in the BAT,which was confirmed by post-mortem tissue analysis.Given the negative regulation of endocannabinoids on the metabolic BAT activity,our study supports the concept that dysregulation of MAGL is likely linked to metabolic disorders.Further,we now provide a suitable imaging tool that allows non-invasive assessment of MAGL in BAT deposits,thereby paving the way for detailed mechanistic studies on the role of BAT in endocannabinoid system(ECS)-related pathologies.