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Curative Radioimmunotherapy of Human Mammary Carcinoma Xenografts with Iodine-131-Labeled Monoclonal Antibodies

Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, and Abteilung Nuklearbiologie, Gesellschaft für Strahlen-und Umweltforschung, Neuherbergx, FRG

Correspondence: For reprints contact: Reingard Senekowitsch, MD, PhD, Nuklearmedizinische Klinik and Poliklinik, Technische Universität München, 8000 München 80, Ismaninger Str. 22, FRG.

ABSTRACT

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 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.