title: A Novel Radiotracer for Imaging Monoacylglycerol Lipase in the Brain Using Positron Emission Tomography.
abstract: Monoacylglycerol lipase (MAGL) is a serine hydrolase that hydrolyzes monoacylglycerols to glycerol and fatty acid and plays an important role in neuroinflammation. MAGL inhibitors are a class of molecules with therapeutic potential for human diseases of the central nervous system (CNS), in areas such as pain and inflammation, immunological disorders, and neurological and psychiatric conditions. Development of a noninvasive imaging probe would elucidate the distribution and functional roles of MAGL in the brain and accelerate medical research and drug discovery in this domain. Herein, we describe the synthesis and pilot rodent imaging of a novel MAGL imaging agent, [(11)C]SAR127303. Our imaging results demonstrate the high specificity, good selectivity, and appropriate kinetics and distribution of [(11)C]SAR127303, validating its utility for imaging MAGL in the brain. Our findings support the translational potential for human CNS MAGL imaging.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, United States.
authors.forename: Changning
authors.initials: C
authors.lastname: Wang
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, United States.|Department of Psychiatry, McLean Imaging Center, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Placzek
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, United States.
authors.forename: Genevieve C
authors.initials: GC
authors.lastname: Van de Bittner
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, United States.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schroeder
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, United States.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000201:enzymology; D002219:Carbamates / Q000138:chemical synthesis / Q000493:pharmacokinetics; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics; D007700:Kinetics; D008297:Male; D008994:Monoacylglycerol Lipases / Q000378:metabolism*; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015898:Tomography Scanners, X-Ray Computed
chemical_list: C000407:4-chlorobenzenesulfonylglycolic acid amide; D000081:Acetamides; D002219:Carbamates; D002247:Carbon Isotopes; D004791:Enzyme Inhibitors; C000602434:SAR127303; D013449:Sulfonamides; D008994:Monoacylglycerol Lipases
keywords: CNS; Monoacylglycerol lipase; PET; brain; radiotracer