Yamasaki_2018_Neuroimage_176_313

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 lambdak3). 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 approximately 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 lambdak3 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.