一种用于食欲素受体神经影像学的新型正电子发射断层扫描探针。
A New Positron Emission Tomography Probe for Orexin Receptors Neuroimaging.
机构信息
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
出版信息
Molecules. 2020 Feb 25;25(5):1018. doi: 10.3390/molecules25051018.
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]CW24) for OXRs in the brain. CW24 has moderate binding affinity for OXRs (IC = 0.253 μM and 1.406 μM for OXR and OXR, respectively) and shows good selectivity to OXRs over 40 other central nervous system (CNS) targets. [C]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]CW24 warrants further evaluation as a PET imaging probe of OXRs in the brain.
食欲素受体（OX）在动机和睡眠-觉醒调节中起着关键作用，在各种情绪障碍中具有有前途的治疗潜力。为了进一步研究食欲素受体（OXR）在活体人脑中的作用，并评估靶向食欲素的治疗药物的治疗潜力，我们在此报告了一种新型的用于大脑中 OXR 的 PET 探针（[C]CW24）。CW24 对 OXR 具有中等的结合亲和力（IC 分别为 0.253 μM 和 1.406 μM），并显示出对 40 多种其他中枢神经系统（CNS）靶标优于 OXR 的良好选择性。[C]CW24 在啮齿动物和非人类灵长类动物中有较高的脑摄取率，良好的代谢稳定性，以及适合用于脑正电子发射断层扫描（PET）成像的分布和药代动力学。[C]CW24 有希望进一步评估为用于大脑中 OXR 的 PET 成像探针。
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