Successful radioimmunotherapy of established syngeneic rat colon carcinoma with 211 At-mAb

Background: Most carcinomas are prone to metastasize despite successful treatment of the primary tumor. One way to address this clinical challenge may be targeted therapy with alpha-emitting radionuclides such as astatine-211 (At-211). Radioimmunotherapy utilizing alpha-particle emitting radionuclides is considered especially suitable for the treatment of small cell clusters and single cells, although lesions of different sizes may also be present in the patient. The aim of this study was primarily to evaluate the toxicity and secondarily in vivo efficacy of a At-211-labeled monoclonal antibody (mAb) directed against colon carcinoma with tumor diameters of approximately 10 mm. Methods: Eighteen rats with subperitoneal syngeneic colon carcinoma were allocated to three groups of six animals together with three healthy rats in each group. The groups were injected intravenously with either 150 mu g of unlabeled mAbs (controls) or 2.5 or 5 MBq At-211-mAbs directed towards the Lewis Upsilon antigen expressed on the cell membrane of several carcinomas. Tumor volume, body weight, and blood cell counts were monitored for 100 days after treatment. Results: Local tumors were non-palpable in five out of six rats after treatment with both activities of At-211-mAbs, compared to one out of six in the control group. At the study end, half of the animals in each group given At-211-BR96 and one animal in the control group were free from disease. Radioimmunotherapy resulted in dose-dependent, transient weight loss and myelotoxicity. Survival was significantly better in the groups receiving targeted alpha therapy than in those receiving unlabeled mAbs. Conclusions: This study demonstrates the possibility of treating small, solid colon carcinoma tumors with alpha-emitting radionuclides such as At-211 bound to mAbs, with tolerable toxicity.