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 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 Ki2-TCMi and λk3 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.

journal_name

Neuroimage

journal_title

NeuroImage

authors

Yamasaki T,Mori W,Zhang Y,Hatori A,Fujinaga M,Wakizaka H,Kurihara Y,Wang L,Nengaki N,Ohya T,Liang SH,Zhang MR

doi

10.1016/j.neuroimage.2018.05.015

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

313-320

eissn

1053-8119

issn

1095-9572

pii

S1053-8119(18)30413-0

journal_volume

176

pub_type

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