TY - JOUR AU - Cheng Ran AU - Fujinaga Masayuki AU - Yang Jing AU - Rong Jian AU - Haider Ahmed AU - Ogasawara Daisuke AU - Van Richard S. AU - Shao Tuo AU - Chen Zhen AU - Zhang Xiaofei AU - Leon Erick R. Calderon AU - Zhang Yiding AU - Mori Wakana AU - Kumata Katsushi AU - Yamasaki Tomoteru AU - Xie Lin AU - Sun Shaofa AU - Wang Lu AU - Ran Chongzhao AU - Shao Yihan AU - Cravatt Benjamin AU - Josephson Lee AU - Zhang Ming-Rong AU - Liang Steven H. PY - 2022 TI - A novel monoacylglycerol lipase-targeted 18F-labeled probe for positron emission tomography imaging of brown adipose tissue in the energy network JF - Acta Pharmacologica Sinica; Vol 43, No 11 (November 2022): Acta Pharmacologica Sinica Y2 - 2022 KW - N2 - 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 [ 18 F]FEPAD. Pharmacokinetics and binding studies on [ 18 F]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 [ 18 F]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. UR - http://www.chinaphar.com/article/view/10720