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

Publication date: 1 August 2018
Source:NeuroImage, Volume 176
Author(s): Tomoteru Yamasaki, Wakana Mori, Yiding Zhang, Akiko Hatori, Masayuki Fujinaga, Hidekatsu Wakizaka, Yusuke Kurihara, Lu Wang, Nobuki Nengaki, Tomoyuki Ohya, Steven H. Liang, Ming-Rong Zhang
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, 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 [¹¹C]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 [¹¹C]SAR127303 reflecting MAGL concentrations in rat brain regions for the first time.



https://ift.tt/2K9hZiV