Relative Therapeutic Efficacy of 125I- and 131I- Labeled Monoclonal Antibody A33 in a Human Colon Cancer Xenograft

A33, a monoclonal antibody that targets colon carcinomas, was labeled with 125I or 131I and the relative therapeutic efficacy of the 2 radiolabeled species was compared in a human colon cancer xenograft system. Methods: Nude mice bearing human SW1222 colon carcinoma xenografts were administered esca-lating activities of 125I-A33 (9.25–148 MBq) or 131I-A33 (0.925– 18.5 MBq), 125I- and 131I-labeled control antibodies, unlabeled antibody, or no antibody. The effects of treatment were as-sessed using the endpoints of tumor growth delay and cure. Results: Tumor growth delay increased with administered ac-tivity for all radiolabeled antibodies. Approximately 4.5 times more activity was required for 125I-A33 to produce therapeutic effects that were equivalent to those of 131I-A33. This ratio was approximately 7 for a nonspecific, noninternalizing isotype-matched, radiolabeled control antibody. Unlabeled A33 anti-body had no effect on tumor growth. Approximately 10 times more activity of 125I-A33 produced toxicity similar to that of 131I-A33, and this ratio fell to approximately 6 for radiolabeled control antibody. Conclusion: Treatment with 125I-A33 resulted in a relative therapeutic gain of approximately 2 compared with 131I-A33 in this experimental system. Key Words: radiolabeled mAb A33; targeting; colon cancer xenograft; therapeutic efficac