An ²¹¹At-labeled Tetrazine for Pretargeted Therapy

Pretargeted radioimmunoimaging has been shown to enhance tumor-to-background ratios by up to 125-fold at early time points, leading to more efficient and less toxic radionuclide therapies, particularly with shorter half-lives such as astatine-211 (²¹¹At). The tetrazine ligation is the most utilized bioorthogonal reaction in these strategies, making tetrazines ideal for ²¹¹At labeling and controlling the biodistribution. We developed a ²¹¹At-labeled pretargeting agent for alpha-radionuclide therapy, achieving a radiochemical yield of approximately 65% and purity over 99%. Our results showed higher tumor-to-blood ratios within the first 24 h compared to directly labeled monoclonal antibodies. This suggests that pretargeted therapy may deliver better tumor doses than conventional methods, although the deastatination observed will need to be addressed in future tetrazine developments.