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A novel monoacylglycerol lipase-targeted 18F-labeled probe for positron emission tomography imaging of brown adipose tissue in the energy network
利用統計を見る
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 cancer. Herein, we developed a reversible MAGL PET ligand, [18F]FEPAD ([18F]4), that is based on a unique 4-piperidinyl azetidine diamide scaffold. The pharmacokinetics and binding specificity revealed an 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 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.
KEYWORDS: monoacylglycerol lipase (MAGL); positron emission tomography (PET); diagnostic imaging; fluorine-18; brown adipose tissue (BAT)
A novel monoacylglycerol lipase-targeted 18F-labeled probe for positron emission tomography imaging of brown adipose tissue in the energy network
