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

Over 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.