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

New York Branch, Ludwig Institute for Cancer Research, New York; and Department of Medical Physics, and Nuclear Medicine Service, and Clinical Immunology Service, Memorial Sloan-Kettering Cancer Center, New York, New York

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 escalating 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 assessed using the endpoints of tumor growth delay and cure. Results: Tumor growth delay increased with administered activity 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 antibody 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 efficacy

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