Anti-CD45 radioimmunotherapy using (211)At with bone marrow transplantation prolongs survival in a disseminated murine leukemia model

Blood. 2013 May 2;121(18):3759-67. doi: 10.1182/blood-2012-11-467035. Epub 2013 Mar 7.


Despite aggressive chemotherapy combined with hematopoietic stem cell transplantation (HSCT), many patients with acute myeloid leukemia (AML) relapse. Radioimmunotherapy (RIT) using monoclonal antibodies labeled with β-emitting radionuclides has been explored to reduce relapse. β emitters are limited by lower energies and nonspecific cytotoxicity from longer path lengths compared with α emitters such as (211)At, which has a higher energy profile and shorter path length. We evaluated the efficacy and toxicity of anti-CD45 RIT using (211)At in a disseminated murine AML model. Biodistribution studies in leukemic SJL/J mice showed excellent localization of (211)At-anti-murine CD45 mAb (30F11) to marrow and spleen within 24 hours (18% and 79% injected dose per gram of tissue [ID/g], respectively), with lower kidney and lung uptake (8.4% and 14% ID/g, respectively). In syngeneic HSCT studies, (211)At-B10-30F11 RIT improved the median survival of leukemic mice in a dose-dependent fashion (123, 101, 61, and 37 days given 24, 20, 12, and 0 µCi, respectively). This approach had minimal toxicity with nadir white blood cell counts >2.7 K/µL 2 weeks after HSCT and recovery by 4 weeks. These data suggest that (211)At-anti-CD45 RIT in conjunction with HSCT may be a promising therapeutic option for AML.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Astatine / therapeutic use*
  • Bone Marrow Transplantation*
  • Combined Modality Therapy / methods
  • Disease Models, Animal
  • Female
  • Leukemia / mortality
  • Leukemia / pathology
  • Leukemia / radiotherapy
  • Leukemia / therapy*
  • Leukocyte Common Antigens / immunology*
  • Mice
  • Neoplasm Metastasis
  • Radioimmunotherapy / methods*
  • Survival Analysis
  • Tissue Distribution
  • Treatment Outcome
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • Leukocyte Common Antigens
  • Astatine