A New Positron Emission Tomography Probe for Orexin Receptors Neuroimaging

被引：14

作者：

Bai, Ping ^{[1
,2
,3
]}

Bai, Sha ^{[2
]}

Placzek, Michael S. ^{[2
]}

Lu, Xiaoxia ^{[1
]}

Fiedler, Stephanie A. ^{[2
]}

Ntaganda, Brenda ^{[2
]}

Wey, Hsiao-Ying ^{[2
]}

Wang, Changning ^{[2
]}

机构：

[1] Chinese Acad Sci, Chengdu Inst Biol, Chengdu 610041, Peoples R China

[2] Harvard Med Sch, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA

[3] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

来源：

MOLECULES | 2020年 / 25卷 / 05期

基金：

美国国家卫生研究院;

关键词：

orexin receptors; PET; radiotracer; imaging; ANTAGONIST SB-649868; SLEEP; RADIOTRACER; DISCOVERY; STRESS; POTENT; RADIOSYNTHESIS; HYPOCRETIN; EXPRESSION; PROMOTES;

D O I：

10.3390/molecules25051018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The orexin receptor (OX) is critically involved in motivation and sleep-wake regulation and holds promising therapeutic potential in various mood disorders. To further investigate the role of orexin receptors (OXRs) in the living human brain and to evaluate the treatment potential of orexin-targeting therapeutics, we herein report a novel PET probe ([C-11]CW24) for OXRs in the brain. CW24 has moderate binding affinity for OXRs (IC50 = 0.253 mu M and 1.406 mu M for OX1R and OX2R, respectively) and shows good selectivity to OXRs over 40 other central nervous system (CNS) targets. [C-11]CW24 has high brain uptake in rodents and nonhuman primates, suitable metabolic stability, and appropriate distribution and pharmacokinetics for brain positron emission tomography (PET) imaging. [C-11]CW24 warrants further evaluation as a PET imaging probe of OXRs in the brain.

引用

页数：10

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