An <sup>211</sup>At-labeled Tetrazine for Pretargeted Therapy
Matthias M. Herth, Lars Hvass, Christian B. M. Poulie, Marius Müller, Rocío García‐Vázquez, Tobias Gustavsson, Vladimir Shalgunov, Anne Skovsbo Clausen, Jesper Tranekjær Jørgensen, Ellinor Hansson, Holger Jensen, Emma Aneheim, Sture Lindegren, Andreas Kjær, Umberto Maria Battisti
Abstract
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 ( 211 At). The tetrazine ligation is the most utilized bioorthogonal reaction in these strategies, making tetrazines ideal for 211 At labeling and controlling the biodistribution. We developed a 211 At-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.