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

Sophie Eriksson, Erika Elgström, Tom Bäck, Tomas G Ohlsson, Holger Jensen, Rune Nilsson, Sture Lindegren, Jan Tennvall

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Abstract Alpha-particle emitters, such as astatine-211 ((211)At), 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 ((177)Lu), 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 (177)Lu-labeled antibody, followed by a (211)At-labeled antibody 25 days later. Methods: Rats bearing solid colon carcinoma tumors were treated with 400 MBq/kg body weight (177)Lu-BR96. After 25 days, three groups of animals were given either 5 or 10 MBq/kg body weight of (211)At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any (211)At-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 (211)At-labeled antibodies did not reduce the proportion of animals developing metastases. The rats suffered from reversible myelotoxicity after treatment. Conclusions: Sequential administration of (177)Lu-BR96 and (211)At-BR96 resulted in tolerable toxicity providing halogen blocking but did not enhance the therapeutic effect.
Original languageEnglish
Pages (from-to)238-246
JournalCancer Biotherapy & Radiopharmaceuticals
Issue number6
Publication statusPublished - 2014

Subject classification (UKÄ)

  • Cancer and Oncology


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