A Review of Molecular Imaging of Glutamate Receptors.
A Review of Molecular Imaging of Glutamate Receptors.
复制标题
DOI：
10.3390/molecules25204749
复制
发表时间：
2020-10-16
期刊：
影响因子：
--
通讯作者：
Cumming P
中科院分区：
文献类型：
--
作者：
Kim JH;Marton J;Ametamey SM;Cumming P
正电子发射断层扫描(PET)和单光子发射计算机断层扫描(SPECT)的分子成像技术是一种成熟和重要的活体成像技术，用于评估基本的生物学过程和揭示神经递质受体在各种神经精神疾病中的作用。特定的配体可用于多巴胺、5-羟色胺和阿片受体的PET/SPECT研究，但针对哺乳动物大脑中主要兴奋性神经递质谷氨酸受体的相应放射性示踪剂的开发一直滞后。尽管谷氨酸神经传递在大脑生理学和中风、癫痫、精神分裂症和神经退行性疾病等疾病中具有核心重要性，但这种情况一直存在。近年来，人们在开发亲离子受体(N-甲基-D-天冬氨酸(NMDA)、红藻氨酸和AMPA/Quisqualate受体)和亲代谢型谷氨酸受体(I、II和III型mGluRs)亚型的分子成像方面进行了广泛的努力。我们现在综述用于谷氨酸受体成像的放射性配体的发展状况，重点放在可用于可靠的体内应用的配体的适用性上。我们简要介绍了所选分子的放射合成方法。总的来说，除了NMDA受体的GluN2B亚基的配体外，用于显示离子型谷氨酸受体的放射性示踪剂的开发几乎没有成功；PCP/MK801结合位点的配体在体内的失败无疑与它们对离子通道开放、畅通状态的依赖有关。许多在体外具有良好结合性能的AMPA和海人藻酸钾受体配体在活体大脑中未能产生可测量的特异性结合。这可能反映了为氨基酸受体开发脑穿透配体的挑战，再加上体内构象的差异。在mGluR成像方面，情况更好，特别是对于mGluR5亚型。几种成功的PET配体用于研究精神分裂症、抑郁症、药物滥用和衰老等情况下的mGluRs。考虑到谷氨酸能信号在脑功能中的中心性和多样性，目前用于离子型和代谢型谷氨酸受体分子成像的选择性和灵敏工具相对较少。进一步针对谷氨酸受体特定亚型和亚基的放射性药物研究可能会开辟新的研究前景，在基础和临床研究中具有广泛的应用前景。
Molecular imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) is a well-established and important in vivo technique to evaluate fundamental biological processes and unravel the role of neurotransmitter receptors in various neuropsychiatric disorders. Specific ligands are available for PET/SPECT studies of dopamine, serotonin, and opiate receptors, but corresponding development of radiotracers for receptors of glutamate, the main excitatory neurotransmitter in mammalian brain, has lagged behind. This state of affairs has persisted despite the central importance of glutamate neurotransmission in brain physiology and in disorders such as stroke, epilepsy, schizophrenia, and neurodegenerative diseases. Recent years have seen extensive efforts to develop useful ligands for molecular imaging of subtypes of the ionotropic (N-methyl-D-aspartate (NMDA), kainate, and AMPA/quisqualate receptors) and metabotropic glutamate receptors (types I, II, and III mGluRs). We now review the state of development of radioligands for glutamate receptor imaging, placing main emphasis on the suitability of available ligands for reliable in vivo applications. We give a brief account of the radiosynthetic approach for selected molecules. In general, with the exception of ligands for the GluN2B subunit of NMDA receptors, there has been little success in developing radiotracers for imaging ionotropic glutamate receptors; failure of ligands for the PCP/MK801 binding site in vivo doubtless relates their dependence on the open, unblocked state of the ion channel. Many AMPA and kainite receptor ligands with good binding properties in vitro have failed to give measurable specific binding in the living brain. This may reflect the challenge of developing brain-penetrating ligands for amino acid receptors, compounded by conformational differences in vivo. The situation is better with respect to mGluR imaging, particularly for the mGluR5 subtype. Several successful PET ligands serve for investigations of mGluRs in conditions such as schizophrenia, depression, substance abuse and aging. Considering the centrality and diversity of glutamatergic signaling in brain function, we have relatively few selective and sensitive tools for molecular imaging of ionotropic and metabotropic glutamate receptors. Further radiopharmaceutical research targeting specific subtypes and subunits of the glutamate receptors may yet open up new investigational vistas with broad applications in basic and clinical research.
登录
查看更多内容
影响因子：
1.8
作者：
Chen, Jiahui;Gan, Jiefeng;Liang, Steven H.
通讯作者：
Liang, Steven H.
影响因子：
8.6
作者：
Charvin, Delphine;Di Paolo, Therese;Conquet, Francois
通讯作者：
Conquet, Francois
影响因子：
10.6
作者：
Bressan, RA;Erlandsson, K;Pilowsky, LS
通讯作者：
Pilowsky, LS
影响因子：
9.3
作者：
Ceccarini, Jenny;Leurquin-Sterk, Gil;Van Laere, Koen
通讯作者：
Van Laere, Koen
影响因子：
3.1
作者：
Ametamey, SM;Bruehlmeier, M;Schubiger, PA
通讯作者：
Schubiger, PA