Prospects of click chemistry reactions in nuclear medicine: the TCO-Tz reaction based on the IEDDA mechanism

Click chemistry reactions, characterized by their high efficiency, strong selectivity, unique in vivo pre-targeting capabilities, and bioorthogonality, have shown great promise in nuclear medicine in recent years. In particular, the trans-cyclooctene (TCO)-tetrazine (Tz) reaction, based on the inverse electron demand Diels-Alder (IEDDA) mechanism, has garnered increasing attention due to its significant advantages in the synthesis and bioconjugation of radiopharmaceuticals. The advancement of nuclear medicine currently faces multiple challenges, including low synthesis efficiency of radiopharmaceuticals, insufficient specificity, and poor biocompatibility. The introduction of click chemistry offers new strategies to address these issues. This paper aims to introduce the fundamental principles of click chemistry and the unique features of the IEDDA mechanism, analyze the specific applications of the TCO-Tz reaction in medical imaging and targeted therapy, and explore its potential applications and future directions in nuclear medicine research.