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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jurcic, J. G. Articles by Scheinberg, D. A. Search for Related Content PubMed PubMed Citation Articles by Jurcic, J. G. Articles by Scheinberg, D. A. Related Collections Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 August 2002, Vol. 100, No. 4, pp. 1233-1239 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Targeted  particle immunotherapy for myeloid leukemia Joseph G. Jurcic, Steven M. Larson, George Sgouros, Michael R. McDevitt, Ronald D. Finn, Chaitanya R. Divgi, Åse M. Ballangrud, Klaus A. Hamacher, Dangshe Ma, John L. Humm, Martin W. Brechbiel, Roger Molinet, and David A. Scheinberg From the Departments of Medicine, Radiology, and Medical Physics and the Molecular Pharmacology and Therapeutics Program, Memorial Sloan-Kettering Cancer Center and the Weill Medical College of Cornell University, New York, NY; the Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; and the European Commission, Joint Research Center, Institute for Transuranium Elements, Karlsruhe, Germany. Unlike  particle-emitting isotopes,  emitters can selectively kill individual cancer cells with a single atomic decay. HuM195, a humanized anti-CD33 monoclonal antibody, specifically targets myeloid leukemia cells and has activity against minimal disease. When labeled with the -emitters 131I and 90Y, HuM195 can eliminate large leukemic burdens in patients, but it produces prolonged myelosuppression requiring hematopoietic stem cell transplantation at high doses. To enhance the potency of native HuM195 yet avoid the nonspecific cytotoxicity of -emitting constructs, the -emitting isotope 213Bi was conjugated to HuM195. Eighteen patients with relapsed and refractory acute myelogenous leukemia or chronic myelomonocytic leukemia were treated with 10.36 to 37.0 MBq/kg 213Bi-HuM195. No significant extramedullary toxicity was seen. All 17 evaluable patients developed myelosuppression, with a median time to recovery of 22 days. Nearly all the 213Bi-HuM195 rapidly localized to and was retained in areas of leukemic involvement, including the bone marrow, liver, and spleen. Absorbed dose ratios between these sites and the whole body were 1000-fold greater than those seen with -emitting constructs in this antigen system and patient population. Fourteen (93%) of 15 evaluable patients had reductions in circulating blasts, and 14 (78%) of 18 patients had reductions in the percentage of bone marrow blasts. This study demonstrates the safety, feasibility, and antileukemic effects of 213Bi-HuM195, and it is the first proof-of-concept for systemic targeted  particle immunotherapy in humans. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Song, K. Shahverdi, D. L. Huso, C. Esaias, J. Fox, A. Liedy, Z. Zhang, R. T. Reilly, C. Apostolidis, A. Morgenstern, et al. 213Bi ({alpha}-Emitter)-Antibody Targeting of Breast Cancer Metastases in the neu-N Transgenic Mouse Model Cancer Res., May 15, 2008; 68(10): 3873 - 3880. [Abstract] [Full Text] [PDF] M. R. Zalutsky, D. A. Reardon, G. Akabani, R. E. Coleman, A. H. Friedman, H. S. Friedman, R. E. McLendon, T. Z. Wong, and D. D. 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