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

• Published in: Blood 2013-05, Vol.121 (18), p.3759
• Main Authors: Orozco, Johnnie J, Bäck, Tom, Kenoyer, Aimee, Balkin, Ethan R, Hamlin, Donald K, Wilbur, D Scott, Fisher, Darrell R, Frayo, Shani L, Hylarides, Mark D, Green, Damian J, Gopal, Ajay K, Press, Oliver W, Pagel, John M
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 1528-0020
• DOI: 10.1182/blood-2012-11-467035

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.