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, [ 11 C]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 [ 11 C]SAR127303. An irreversible two-tissue compartment model (2-TCMi, k 4  = 0) analysis was conducted to estimate quantitative parameters ( k 3 , K i 2-TCMi , and λk 3 ). These parameters were successfully obtained with high identifiability (  striatum > hippocampus > thalamus > cerebellum > hypothalamus ≈ pons. In vitro autoradiographs using [ 11 C]SAR127303 showed a heterogeneous distribution of radioactivity, as seen in the PET images. The K i 2-TCMi and λk 3 values correlated relatively highly with in vitro binding ( r  > 0.4, P K i 2-TCMi values showed high correlation and low underestimation ( K i Patlak ). In conclusion, we successfully estimated regional net uptake value of [ 11 C]SAR127303 reflecting MAGL concentrations in rat brain regions for the first time.