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¹³¹I Radioimmunotherapy and Fractionated External Beam Radiotherapy: Comparative Effectiveness in a Human Tumor Xenograft

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

Correspondence: For correspondence or reprints contact: Els C. Barendswaard, MD, Leukemia Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021.

ABSTRACT

This article compares the effectiveness of radiation delivered by a radiolabeled monoclonal antibody, ¹³¹I-labeled A33, that targets colorectal carcinoma, with that of 10 fractions of conventional 320 kV_p x-rays. Methods: Human colorectal cancer xenografts (SW1222) ranging between 0.14 and 0.84 g were grown in nude mice. These were treated either with escalating activities (3.7–18.5 MBq) of ¹³¹I-labeled A33 or 10 fractions of 320 kVp x-rays (fraction sizes from 1.5 to 5 Gy). Tumor dosimetry was determined from a similar group of tumor-bearing animals by serial kill, tumor resection and counting of radioactivity in a gamma counter. The relative effectiveness of the two radiation therapy treatment approaches was compared in terms of tumor regrowth delay and probability of tumor cure. Results: The absorbed dose to tumor per MBq administered was estimated as 3.7 Gy (±1 Gy; 95% confidence interval). We observed a close to linear increase in tumor regrowth delay with escalating administered activity. Equitumor response of ¹³¹I monoclonal antibody A33 was observed at average radiation doses to the tumor three times greater than when delivered by fractionated external beam radiotherapy. The relationship between the likelihood of tumor cure and administered activity was less predictable than that for regrowth delay. Conclusion: The relative effectiveness per unit dose of radiation therapy delivered by ¹³¹I-labeled A33 monoclonal antibodies was approximately one third of that produced by fractionated external beam radiotherapy, when measured by tumor regrowth delay.

Key Words: radioimmunotherapy • radiotherapy • colon cancer xenograft • tumor response • monoclonal antibody A33

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