Pretargeted nuclear imaging and radioimmunotherapy based on the inverse electron-demand Diels-Alder reaction

As a promising approach, in vivo pretargeting can leverage the unique tumor-targeting properties of antibodies for nuclear imaging and therapy while bypassing their pharmacokinetic limitations. The core premise of pretargeting is that targeted vectors and radioisotopes are administered separately, leading to a higher target background ratio than traditional imaging methods using long-lived radionuclides. This strategy directly relies on chemical reactions, namely bioorthogonal reactions. The inverse electron-demand Diels-Alder (IEDDA) cycloaddition between 1, 2, 4, 5-tetrazine and strained alkene dienophile is an emerging catalyst-free 'click' chemistry. The IEDDA reaction has been used in various chemical environments because of its selectivity, efficiency, cleanliness, biocompatibility, and bioorthogonality. In the present review, we briefly focused on the IEDDA reaction in pretargeted nuclear imaging and radioimmunotherapy and discussed the common bioorthogonal click reactions in vivo systems.