靶向多巴胺D3受体PET分子探针的研究进展

Research Progress of PET Molecular Probes Targeting Dopamine D3 Receptor

多巴胺D3受体与药物成瘾、帕金森病(PD)、精神分裂症等神经精神疾病息息相关。以多巴胺D3受体为靶点的PET显像剂可以无创地显示受体密度和状态的变化,从而揭示疾病的起源与发展过程并为治疗提供依据。然而,由于多巴胺D3受体与D2受体有高度相似性,现有D3受体PET显像剂却普遍存在与D2受体选择性不强的问题,限制了D3受体在神经网络中作用机制的研究。因此开发特异性强、亲和性高、选择性高的D3受体探针对中枢神经系统疾病的诊断与治疗意义重大。本研究对^(18)F和^(11)C标记的四氢吡咯烷类、氨基四氢萘类、苯基哌嗪类PET分子探针进行综述,并讨论D3受体探针开发面对的挑战,以期为未来探针开发提供帮助。

Dopamine D3 receptors are closely related to drug addiction,Parkinson’s disease(PD),schizophrenia and other neuropsychiatric diseases.PET imaging agents that target dopamine D3 receptors can noninvasively show changes in receptor density and status,thus revealing the origin and development process of disease and providing a basis for treatment.However,because dopamine D3 receptors have high similarity with D2 receptors hinders the selectivity of existing D3 receptors PET imaging agents,which limits the study of the mechanism of action of dopamine D3 receptors in neural networks.It is of great significance to develop high specificity,affinity,selective D3 receptor probe for the diagnosis and treatment of diseases of the central nervous system.This article reviewed the ^(18)F and ^(11)C radiolabeled PET molecular probes including tetrahydropyrrole derivatives,aminotetralin derivatives and phenylpiperazines derivatives.Furthermore,the challenges in the development of D3 receptor probes also be discussed,aiming to provide valuable insights for future probe advancements.