Garvan Institute of Medical Research, 384 Victoria St, NSW 2010, Australia.
School of Chemistry, The University of Sydney, NSW 2006, Australia.
Nucl Med Biol. 2022 Nov-Dec;114-115:108-120. doi: 10.1016/j.nucmedbio.2022.04.001. Epub 2022 Apr 6.
This review outlines small molecule radiotracers developed for positron emission tomography (PET) imaging of proteinopathies, neurodegenerative diseases characterised by accumulation of malformed proteins, over the last two decades with the focus on radioligands that have progressed to clinical studies. Introduction provides a short summary of proteinopathy targets used for PET imaging, including vastly studied proteins Aβ and tau and emerging α-synuclein. In the main section, clinically relevant Aβ and tau radioligand classes and their properties are discussed, including an overview of lead compounds and radioligand candidates studied as α-synuclein imaging agents in the early discovery and preclinical development phase. Lastly, the specific challenges and future directions in proteinopathy radioligand development are summarized.
这篇综述概述了过去二十年中开发用于正电子发射断层扫描 (PET) 成像的小分子放射性示踪剂,重点是已进展到临床研究的放射性配体。引言部分简要总结了用于 PET 成像的蛋白病变靶点,包括广泛研究的 Aβ 和 tau 蛋白以及新兴的 α-突触核蛋白。在主要部分中,讨论了临床相关的 Aβ 和 tau 放射性配体类别及其特性,包括概述了在早期发现和临床前开发阶段作为 α-突触核蛋白成像剂研究的先导化合物和放射性配体候选物。最后,总结了蛋白病变放射性配体开发中的具体挑战和未来方向。