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

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

doi:10.1016/j.neuroimage.2018.05.015

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

Neuroimage. 2018 Aug 1:176:313-320. doi: 10.1016/j.neuroimage.2018.05.015. Epub 2018 May 5.

Authors

Affiliations

¹ National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan. Electronic address: yamasaki.tomoteru@qst.go.jp.
² National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
³ National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan; SHI Accelerator Service Co. Ltd, 1-17-6 Osaki, Shinagawa-ku, Tokyo, 141-0032, Japan.
⁴ Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, 510630, China; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital & Harvard Medical School, Boston, MA, 02114, USA.
⁵ Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital & Harvard Medical School, Boston, MA, 02114, USA.

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, K_i^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 K_i^2-TCMi and λk₃ values correlated relatively highly with in vitro binding (r > 0.4, P < 0.005). The K_i^2-TCMi values showed high correlation and low underestimation (<10%) compared with the slope of a Patlak plot analysis with linear regression (K_i^Patlak). In conclusion, we successfully estimated regional net uptake value of [¹¹C]SAR127303 reflecting MAGL concentrations in rat brain regions for the first time.

Keywords: Monoacylglycerol lipase; Net influx constant K(i); Patlak plot; Positron emission tomography; Two-tissue compartment model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / diagnostic imaging*
Brain / metabolism*
Carbamates
Carbon Radioisotopes
Male
Models, Theoretical*
Monoacylglycerol Lipases / metabolism*
Neuroimaging / methods*
Positron-Emission Tomography / methods*
Rats
Rats, Sprague-Dawley
Sulfonamides

Substances

Carbamates
Carbon Radioisotopes
Carbon-11
SAR127303
Sulfonamides
Monoacylglycerol Lipases

Abstract

Publication types

MeSH terms

Substances

Grants and funding