The exceptional speed and biorthogonality of the inverse electron-demand Diels-Alder (IEDDA) click chemistry between 1,2,4,5-tetrazines and strained alkene dienophiles have made it promising in the realm of pretargeted imaging and therapy. During the past 10 years, the IEDDA-pretargeted strategies have been tested and have already proven capable of producing images with high tumor-to-background ratios and improving therapeutic effect. This review will focus on recent applications of click chemistry ligations in the pretargeted imaging studies of single photon emission computed tomography (SPECT), positron emission tomography (PET), and pretargeted radioimmunotherapy investigations. Additionally, the influence factors of stability, reactivity, and pharmacokinetic properties of TCO tag modified immunoconjugates and radiolabeled Tz derivatives were also summarized in this article, which should be carefully considered in the system design in order to develop a successful pretargeted methodology. We hope that this review will not only equip readers with a knowledge of pretargeted methodology based on IEDDA click chemistry but also inspire synthetic chemists and radiochemists to develop pretargeted radiopharmaceutical components in a more innovative way with various influence factors considered.

中文翻译：

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基于逆电子需求Diels-Alder反应和预靶向合成设计中的关键因素的预靶向核显像和放射免疫疗法。

1,2,4,5-四嗪和应变烯烃双亲二烯体之间的逆电子需求Diels-Alder（IEDDA）点击化学的非凡速度和生物正交性使其在预靶向成像和治疗领域大有希望。在过去的10年中，对IEDDA预先确定的策略进行了测试，并且已经证明能够产生具有高肿瘤与背景比率的图像并改善治疗效果。这项审查将侧重于单击化学结扎技术在单光子发射计算机断层扫描（SPECT），正电子发射断层扫描（PET）和预定位放射免疫疗法研究的预定位成像研究中的最新应用。此外，稳定性，反应性，本文还概述了TCO标签修饰的免疫偶联物和放射性标记的Tz衍生物的药代动力学特性，在系统设计中应仔细考虑这些因素，以开发成功的预靶向方法。我们希望这篇评论不仅可以使读者了解基于IEDDA点击化学的预靶向方法学知识，而且可以启发合成化学家和放射化学家以更具创新性的方式开发出具有多种考虑因素的预靶向放射性药物成分。