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The Anti-CD25 Monoclonal Antibody 7G7/B6, Armed with the -Emitter ²¹¹At, Provides Effective Radioimmunotherapy for a Murine Model of Leukemia

¹ Metabolism Branch and ² Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, and ³ PET and Nuclear Medicine Department, Clinical Center, NIH, Bethesda, Maryland

Requests for reprints: Thomas A. Waldmann, Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Building 10, Room 4N115, 10 Center Drive, Bethesda, MD 20892-1374. Phone: 301-496-6656; Fax: 301-496-9956; E-mail: tawald{at}helix.nih.gov.

Radioimmunotherapy of cancer with radiolabeled antibodies has shown promise. -Particles are very attractive for cancer therapy, especially for isolated malignant cells, as is observed in leukemia, because of their high linear energy transfer and short effective path length. We evaluated an anti-CD25 [interleukin-2 receptor (IL-2R)] monoclonal antibody, 7G7/B6, armed with ²¹¹At as a potential radioimmunotherapeutic agent for CD25-expressing leukemias and lymphomas. Therapeutic studies were done in severe combined immunodeficient/nonobese diabetic mice bearing the karpas299 leukemia and in nude mice bearing the SUDHL-1 lymphoma. The results from a pharmacokinetic study showed that the clearance of ²¹¹At-7G7/B6 from the circulation was virtually identical to ¹²⁵I-7G7/B6. The biodistributions of ²¹¹At-7G7/B6 and ¹²⁵I-7G7/B6 were also similar with the exception of a higher stomach uptake of radioactivity with ²¹¹At-7G7/B6. Therapy using 15 µCi of ²¹¹At-7G7/B6 prolonged survival of the karpas299 leukemia–bearing mice significantly when compared with untreated mice and mice treated with ²¹¹At-11F11, a radiolabeled nonspecific control antibody (P < 0.01). All of the mice in the control and ²¹¹At-11F11 groups died by day 46 whereas >70% of the mice in the ²¹¹At-7G7/B6 group still survived at that time. In summary, ²¹¹At-7G7/B6 could serve as an effective therapeutic agent for patients with CD25-expressing leukemias. (Cancer Res 2006; 66(16): 8227-32)

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