Author:

Keywords:

MAGL, [C-11]MA-PB-1, MJN110, Biodistribution, PET imaging, Science & Technology, Life Sciences & Biomedicine, Chemistry, Medicinal, Pharmacology & Pharmacy, POSITRON-EMISSION-TOMOGRAPHY, HIGHLY SELECTIVE INHIBITORS, ENZYMATIC PATHWAYS, HYDROLYSIS, 2-ARACHIDONOYLGLYCEROL, SYSTEM, RECEPTOR, BEARING, POTENT, UREAS, [(11)C]MA-PB-1, Animals, Benzyl Compounds, Brain, Dose-Response Relationship, Drug, Enzyme Inhibitors, Female, Macaca mulatta, Mice, Molecular Structure, Monoacylglycerol Lipases, Piperazines, Positron-Emission Tomography, Radioactive Tracers, Rats, Rats, Wistar, Structure-Activity Relationship, Tissue Distribution, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 1115 Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry, 3214 Pharmacology and pharmaceutical sciences, 3404 Medicinal and biomolecular chemistry, 3405 Organic chemistry

Abstract:

MAGL is a potential therapeutic target for oncological and psychiatric diseases. Our objective was to develop a PET tracer for in vivo quantification of MAGL. We report [11C]MA-PB-1 as an irreversible MAGL inhibitor PET tracer. The in vitro inhibitory activity, ex vivo distribution, brain kinetics and specificity of [11C]MA-PB-1 binding were studied. Ex vivo biodistribution and microPET showed good brain uptake which could be blocked by pretreatment with both MA-PB-1 and a structurally non-related MAGL inhibitor MJN110. These initial results suggest that [11C]MA-PB-1 is a suitable tracer for in vivo imaging of MAGL.