The Inverse Electron Demand Diels‐Alder Reaction Between Tetrazine and Trans‐Cyclooctene for Pretargeted Bioimaging Applications

Abstract

AbstractOver the past few decades, pretargeted bioimaging has made significant contributions to disease diagnosis and the real‐time visualization of biological processes. Notably, the inverse electron demand Diels‐Alder (IEDDA) reaction between tetrazine (Tz) and trans‐cyclooctene (TCO) has shown enormous potential in pretargeted bioimaging applications by capitalizing on its rapid kinetics, specific reactivity, biorthogonality and biocompatibility. To date, imaging probes based on the Tz−TCO click reaction have been extensively developed and widely used for pretargeted bioimaging applications. In this review, we focus on the Tz−TCO click reaction and summarize its applications in pretargeted bioimaging. Firstly, the fundamental principles for designing imaging probes based on the Tz−TCO click reaction are explained. Then, recent advances in imaging probes based on the Tz−TCO click reaction are discussed in detail. Finally, the current challenges and perspectives of the Tz−TCO click reaction in pretargeted bioimaging applications are presented.