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

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, k4  = 0) analysis was conducted to estimate quantitative parameters (k3 , Ki 2-TCMi , and λk3 ). 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 [11 C]SAR127303 showed a heterogeneous distribution of radioactivity, as seen in the PET images. The Ki 2-TCMi and λk3 values correlated relatively highly with in vitro binding (r > 0.4, P < 0.005). The Ki 2-TCMi values showed high correlation and low underestimation (<10%) compared with the slope of a Patlak plot analysis with linear regression (Ki 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.