In Vitro and in Vivo Evaluation of ¹¹C-Labeled Azetidinecarboxylates for Imaging Monoacylglycerol Lipase by PET Imaging Studies.

ABSTRACT: Monoacylglycerol lipase (MAGL) is the principle enzyme for metabolizing endogenous cannabinoid ligand 2-arachidonoyglycerol (2-AG). Blockade of MAGL increases 2-AG levels, resulting in subsequent activation of the endocannabinoid system, and has emerged as a novel therapeutic strategy to treat drug addiction, inflammation, and neurodegenerative diseases. Herein we report a new series of MAGL inhibitors, which were radiolabeled by site-specific labeling technologies, including ¹¹C-carbonylation and spirocyclic iodonium ylide (SCIDY) radiofluorination. The lead compound [¹¹C]10 (MAGL-0519) demonstrated high specific binding and selectivity in vitro and in vivo. We also observed unexpected washout kinetics with these irreversible radiotracers, in which in vivo evidence f

SUBMITTER: Cheng R 

PROVIDER: S-EPMC5966020 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature