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7194207 
Journal Article 
Identification and Development of an Irreversible Monoacylglycerol Lipase (MAGL) Positron Emission Tomography (PET) Radioligand with High Specificity 
Zhang, Lei; Smith, DL; Nason, DM; O'Neil, S; Mcallister, L; Schildknegt, K; Trapa, P; Mccarthy, TJ; Villalobos, A; Halldin, C; Butler, CR; Maresca, KP; Takano, A; Nag, S; Jia, Z; Arakawa, R; Piro, , JR; Samad, T; , 
2019 
Yes 
Journal of Medicinal Chemistry
ISSN: 0022-2623
EISSN: 1520-4804 
AMER CHEMICAL SOC 
WASHINGTON 
62 
18 
8532-8543 
English 
31483137 
WOS:000488334500010 
Monoacylglycerol lipase (MAGL), a serine hydrolase extensively expressed throughout the brain, serves as a key gatekeeper regulating the tone of endocannabinoid signaling. Preclinically, inhibition of MAGL is known to provide therapeutic benefits for a number of neurological disorders. The availability of a MAGL-specific positron emission tomography (PET) ligand would considerably facilitate the development and clinical characterization of MAGL inhibitors via noninvasive and quantitative PET imaging. Herein, we report the identification of the potent and selective irreversible MAGL inhibitor 7 (PF-06809247) as a suitable radioligand lead, which upon radiolabeling was found to exhibit a high level of MAGL specificity; this enabled cross-species measurement of MAGL brain expression (B-max), assessment of in vivo binding in the rat, and nonhuman primate PET imaging.