Identification of (R)-[18F]YH134 for Monoacylglycerol Lipase Neuroimaging and Exploration of Its Use for Central Nervous System and Peripheral Drug Development

单酰甘油脂肪酶 化学 药理学 中枢神经系统 神经科学 医学 生物 生物化学 内大麻素系统 受体
作者
Yong He,Stefanie D. Krämer,Uwe Grether,Matthias Wittwer,Ludovic Collin,Bernd Kuhn,Andreas Topp,Dominik Heer,Fionn O’Hara,Michael Honer,Anto Pavlovic,Hans G. Richter,Martin Ritter,Didier Rombach,Claudia Keller,Luca Gobbi,Linjing Mu
出处
期刊:The Journal of Nuclear Medicine [Society of Nuclear Medicine and Molecular Imaging]
卷期号:65 (2): 300-305 被引量:1
标识
DOI:10.2967/jnumed.123.266426
摘要

This study aimed to evaluate (R)-[18F]YH134 as a novel PET tracer for imaging monoacylglycerol lipase (MAGL). Considering the ubiquitous expression of MAGL throughout the whole body, the impact of various MAGL inhibitors on (R)-[18F]YH134 brain uptake and its application in brain-periphery crosstalk were explored. Methods: MAGL knockout and wild-type mice were used to evaluate (R)-[18F]YH134 in in vitro autoradiography and PET experiments. To explore the impact of peripheral MAGL occupancy on (R)-[18F]YH134 brain uptake, PET kinetics with an arterial input function were studied in male Wistar rats under baseline and blocking conditions. Results: In in vitro autoradiography, (R)-[18F]YH134 revealed a heterogeneous distribution pattern with high binding to MAGL-rich brain regions in wild-type mouse brain slices, whereas the radioactive signal was negligible in MAGL knockout mouse brain slices. The in vivo brain PET images of (R)-[18F]YH134 in wild-type and MAGL knockout mice demonstrated its high specificity and selectivity in mouse brain. A Logan plot with plasma input function was applied to estimate the distribution volume (VT) of (R)-[18F]YH134. VT was significantly reduced by a brain-penetrant MAGL inhibitor but was unchanged by a peripherally restricted MAGL inhibitor. The MAGL target occupancy in the periphery was estimated using (R)-[18F]YH134 PET imaging data from the brain. Conclusion: (R)-[18F]YH134 is a highly specific and selective PET tracer with favorable kinetic properties for imaging MAGL in rodent brain. Our results showed that blocking of the peripheral target influences brain uptake but not the VT of (R)-[18F]YH134. (R)-[18F]YH134 can be used for estimating the dose of MAGL inhibitor at half-maximal peripheral target occupancy.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
支尔柳完成签到,获得积分10
刚刚
领导范儿应助ly采纳,获得10
刚刚
刚刚
丁凛完成签到,获得积分10
刚刚
1秒前
茉莉茉莉轰完成签到,获得积分10
1秒前
偷乐发布了新的文献求助10
1秒前
1秒前
2秒前
GG发布了新的文献求助10
2秒前
2秒前
拼搏剑心完成签到 ,获得积分10
2秒前
Aonlyhuang发布了新的文献求助10
2秒前
传奇3应助xuzj采纳,获得30
3秒前
JamesPei应助XHH1994采纳,获得10
3秒前
4秒前
Jojo发布了新的文献求助30
4秒前
Singularity应助芋孟齐采纳,获得10
5秒前
少年梦完成签到,获得积分20
5秒前
5秒前
yydragen应助QH采纳,获得100
5秒前
6秒前
CodeCraft应助背后海亦采纳,获得10
6秒前
Hello应助背后海亦采纳,获得10
6秒前
6秒前
慕青应助背后海亦采纳,获得20
6秒前
斯文败类应助背后海亦采纳,获得10
6秒前
1351567822应助背后海亦采纳,获得10
6秒前
面壁思过应助背后海亦采纳,获得20
7秒前
所所应助背后海亦采纳,获得10
7秒前
NexusExplorer应助背后海亦采纳,获得10
7秒前
1351567822应助背后海亦采纳,获得10
7秒前
顾矜应助搞怪的凡梦采纳,获得10
7秒前
XUHYBOR发布了新的文献求助10
8秒前
8秒前
8秒前
9秒前
9秒前
kong应助Ellis采纳,获得20
9秒前
10秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3970287
求助须知:如何正确求助?哪些是违规求助? 3515034
关于积分的说明 11176923
捐赠科研通 3250301
什么是DOI,文献DOI怎么找? 1795244
邀请新用户注册赠送积分活动 875732
科研通“疑难数据库(出版商)”最低求助积分说明 805039