Anti-CD45 radioimmunotherapy using 211At with bone marrow transplantation prolongs survival in a disseminated murine leukemia model
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 limite...
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Veröffentlicht in: | Blood 2013-05, Vol.121 (18), p.3759-3767 |
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Sprache: | eng |
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Zusammenfassung: | 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 211At, which has a higher energy profile and shorter path length. We evaluated the efficacy and toxicity of anti-CD45 RIT using 211At in a disseminated murine AML model. Biodistribution studies in leukemic SJL/J mice showed excellent localization of 211At-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, 211At-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 211At-anti-CD45 RIT in conjunction with HSCT may be a promising therapeutic option for AML.
•Astatination of anti-CD45 antibody via a closo-decaborate compound yields a stable conjugate that targets radiation to hematologic organs.•211At-anti-CD45 radioimmunotherapy combined with bone marrow transplantation prolongs survival in a disseminated murine leukemia model. |
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ISSN: | 0006-4971 1528-0020 1528-0020 |
DOI: | 10.1182/blood-2012-11-467035 |