We evaluated the feasibility and therapeutic effectiveness of a DOTA-PRIT approach using a <sup>177</sup>Lu/<sup>225</sup>Ac radioisotope cocktail, directly compared with monotherapies targeting GPA33 in human colorectal cancer (CRC) xenografts in mice.<h4>Methods</h4>A three-step pretargeting regimen was employed: an anti-GPA33/anti-DOTA bispecific antibody (BsAb), a dendrimeric clearing agent, and radioligands labeled with <sup>177</sup>Lu, <sup>225</sup>Ac, alone or in combination. This evidence concerns the gene GPA33 and colorectal cancer.