I-131 radioimmunotherapy and fractionated external beam radiotherapy: Comparative effectiveness in a human tumor xenograft

This article compares the effectiveness of radiation delivered by a radiola beled monoclonal antibody, (131)l-labeled A33, that targets colorectal carc inoma, 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 activi ties (3.7-18.5 MBq) of (131)l-labeled A33 or 10 fractions of 320 kVp x-rays (fraction sizes from 1.5 to 5 Gy). Tumor dosimetry was determined from a s imilar group of tumor-bearing animals by serial kill, tumor resection and c ounting of radioactivity in a gamma counter. The relative effectiveness of the two radiation therapy treatment approaches was compared in terms of tum or 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% confid ence interval). We observed a close to linear increase in tumor regrowth de lay with escalating administered activity. Equi-tumor response of (131)l mo noclonal antibody A33 was observed at average radiation doses to the tumor three times greater than when delivered by fractionated external beam radio therapy, The relationship between the likelihood of tumor cure and administ ered activity was less predictable than that for regrowth delay. Conclusion : The relative effectiveness per unit dose of radiation therapy delivered b y (131)l-labeled A33 monoclonal antibodies was approximately one third of t hat produced by fractionated external beam radiotherapy, when measured by t umor regrowth delay.