DOTA-based pre-targeting of alpha emitters

Antibody-based targeting provides superior specificity for radionuclide therapy. However, it suffers from low absorbed dose compared to external beam radiotherapy and normal tissue toxicity due to the slow circulation and tumor uptake of antibodies. Pre-targeted radioimmunotherapy separates the slow antibody targeting phase from rapid delivery of the radionuclide by small anti-chelate ligands. The goal of this project is to adapt the pre-targeted radioimmunotherapy strategy to the delivery of actinium (Ac)-225, a high linear energy transfer alpha emitter, for the treatment of colorectal and breast cancer.