Sequential Radioimmunotherapy with 177Lu-and 211At-Labeled Monoclonal Antibody BR96 in a Syngeneic Rat Colon Carcinoma Model

Alpha-particle emitters, such as astatine-211 (At-211), are generally considered suitable for the treatment of small cell clusters due to their short path length, while beta-particle emitters, for example, Lutetium-177 (Lu-177), have a longer path length and are considered better for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a Lu-177-labeled antibody, followed by a At-211-labeled antibody 25 days later. Methods: Rats bearing solid colon carcinoma tumors were treated with 400 MBq/kg body weight Lu-177-BR96. After 25 days, three groups of animals were given either 5 or 10 MBq/kg body weight of At-211-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any At-211-BR96. Myelotoxicity, body weight, tumor size, and development of metastases were monitored for 120 days. Results: Tumors were undetectable in 90% of the animals on day 25, independent of treatment. Additional treatment with At-211-labeled antibodies did not reduce the proportion of animals developing metastases. The rats suffered from reversible myelotoxicity after treatment. Conclusions: Sequential administration of Lu-177-BR96 and At-211-BR96 resulted in tolerable toxicity providing halogen blocking but did not enhance the therapeutic effect.