Curative radioimmunotherapy of human mammary carcinoma xenografts with iodine-131-labeled monoclonal antibodies.

The radioiodinated monoclonal antibody BW 495/36 showed an exceptionally high uptake and long residence time in human ductal mammary carcinoma xenografts in nude mice. There was a mean tumor uptake of 82%/g 24 hr p.i., decreasing with a biologic half-life of approximately 6 days, to 15%/g by Day 16. The tumor-to-blood ratio increased from 2.8 to 21.4 and the percentage of the whole-body retention recovered in the tumor from 47% to 80% during the same time interval. The therapeutic efficiency of two injections of 7.4 MBq 131I-BW 495/36 was evaluated by comparing the tumor size with that in mice injected with either the same amount of the unlabeled MoAb, the same radioactivity of an 131I-labeled nonspecific MoAb, or with saline only. The high tumor accumulation of 131I-BW 495/36 led to a total tumor dose of 77 Gy resulting in a mean reduction in tumor diameter of 50%, corresponding to a reduction in tumor volume of 88% within 42 days p.i. Unlabeled MoAb had no effect on tumor growth compared with controls, whereas 131I nonspecific antibody caused a slight inhibition of tumor growth. Histologic tumor sections showed large areas of necrosis and a pronounced vacuolation of the tumor cell cytoplasm between Days 7 and 30 p.i. By Day 42 all remaining tissue in the tumor was identified as mouse connective tissue.