First demonstration of in vivo mapping for regional brain monoacylglycerol lipase using PET with [11C]SAR127303

ABSTRACT Monoacylglycerol lipase (MAGL) is a main regulator of the endocannabinoid system within the central nervous system (CNS). Recently, [11C]SAR127303 was developed as a promising radioligand for MAGL imaging. In this study, we aimed to quantify regional MAGL concentrations in the rat brain using positron emission tomography (PET) with [11C]SAR127303. An irreversible two‐tissue compartment model (2‐TCMi, k4=0) analysis was conducted to estimate quantitative parameters (k3, Ki2‐TCMi, and &lgr;k3). These parameters were successfully obtained with high identifiability (<10 %COV) for the following regions ranked in order from highest to lowest: cingulate cortex>striatum>hippocampus>thalamus>cerebellum>hypothalamus≈pons. In vitro autoradiographs using [11C]SAR127303 showed a heterogeneous distribution of radioactivity, as seen in the PET images. The Ki2‐TCMi and &lgr;k3 values correlated relatively highly with in vitro binding (r>0.4, P<0.005). The Ki2‐TCMi values showed high correlation and low underestimation (<10%) compared with the slope of a Patlak plot analysis with linear regression (KiPatlak). In conclusion, we successfully estimated regional net uptake value of [11C]SAR127303 reflecting MAGL concentrations in rat brain regions for the first time. HIGHLIGHTSCompartment model analysis for PET with [11C]SAR127303 was successfully conducted.Net uptake value of [11C]SAR127303 highly correlated with MAGL concentrations.In vivo mapping for brain MAGL concentration was demonstrated for the first time.