First demonstration of in vivo mapping for regional brain monoacylglycerol lipase using PET with [(11)C]SAR127303.
First demonstration of in vivo mapping for regional brain monoacylglycerol lipase using PET with [(11)C]SAR127303.
复制标题
DOI：
10.1016/j.neuroimage.2018.05.015
复制
发表时间：
2018-08-01
期刊：
影响因子：
5.7
通讯作者：
Zhang MR
中科院分区：
文献类型：
--
作者：
Yamasaki T;Mori W;Zhang Y;Hatori A;Fujinaga M;Wakizaka H;Kurihara Y;Wang L;Nengaki N;Ohya T;Liang SH;Zhang MR
单酰基甘油脂肪酶（MAGL）是中枢神经系统（CNS）内源性大麻素系统的主要调节剂。近年来，[11C]SAR127303被认为是一种很有前途的磁共振成像配体。在这项研究中，我们的目的是使用[11C]SAR127303正电子发射断层扫描（PET）来量化大鼠脑中的区域MAGL浓度。采用不可逆双组织室模型（2-TCMi, k4 = 0）分析，估计定量参数（k3、Ki2-TCMi和λk3）。这些参数成功获得了高可识别性（< 10% COV），以下区域从高到低依次为：扣带皮层>纹状体>海马>丘脑>小脑>下丘脑≈脑桥。使用[11C]SAR127303的体外放射自显像显示放射性分布不均，如PET图像所示。Ki2-TCMi和λk3值与体外结合相关性较高（r >.4, P < 0.005）。与线性回归（KiPatlak）图斜率分析相比，Ki2-TCMi值具有高相关性和低低估（< 10%）。综上所述，我们首次成功估算了反映大鼠脑区MAGL浓度的[11C]SAR127303的区域净吸收值。
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.
登录
查看更多内容
影响因子：
3.7
作者：
Bolcaen, Julie;Lybaert, Kelly;Goethals, Ingeborg
通讯作者：
Goethals, Ingeborg
影响因子：
5.7
作者：
Ohya, Tomoyuki;Okamura, Toshimitsu;Kikuchi, Tatsuya
通讯作者：
Kikuchi, Tatsuya
影响因子：
3.1
作者：
Hicks JW;Parkes J;Tong J;Houle S;Vasdev N;Wilson AA
通讯作者：
Wilson AA
影响因子：
7.3
作者：
Cheng R;Mori W;Ma L;Alhouayek M;Hatori A;Zhang Y;Ogasawara D;Yuan G;Chen Z;Zhang X;Shi H;Yamasaki T;Xie L;Kumata K;Fujinaga M;Nagai Y;Minamimoto T;Svensson M;Wang L;Du Y;Ondrechen MJ;Vasdev N;Cravatt BF;Fowler C;Zhang MR;Liang SH
通讯作者：
Liang SH
影响因子：
6.3
作者：
KOEPPE, RA;HOLTHOFF, VA;KUHL, DE
通讯作者：
KUHL, DE