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Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2001-12-0322. This Article Full Text Full Text (PDF) All Versions of this Article: 2001-12-0322v1 100/1/318    most recent 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 Sandmaier, B. M. Articles by Storb, R. Search for Related Content PubMed PubMed Citation Articles by Sandmaier, B. M. Articles by Storb, R. Related Collections Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2002, Vol. 100, No. 1, pp. 318-326 TRANSPLANTATION Bismuth 213-labeled anti-CD45 radioimmunoconjugate to condition dogs for nonmyeloablative allogeneic marrow grafts Brenda M. Sandmaier, Wolfgang A. Bethge, D. Scott Wilbur, Donald K. Hamlin, Erlinda B. Santos, Martin W. Brechbiel, Darrell R. Fisher, and Rainer Storb From the Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; the Departments of Medicine and Radiation Oncology, University of Washington, Seattle; the National Cancer Institute, National Institutes of Health, Bethesda, MD; and Pacific Northwest National Laboratory, Richland, WA. To lower treatment-related mortality and toxicity of conventional marrow transplantation, a nonmyeloablative regimen using 200 cGy total-body irradiation (TBI) and mycophenolate mofetil (MMF) combined with cyclosporine (CSP) for postgrafting immunosuppression was developed. To circumvent possible toxic effects of external-beam  irradiation, strategies for targeted radiation therapy were investigated. We tested whether the short-lived (half-life, 46 minutes) -emitter bismuth 213 (213Bi) conjugated to an anti-CD45 monoclonal antibody (mAb) could replace 200 cGy TBI and selectively target hematopoietic tissues in a canine model of nonmyeloablative DLA-identical marrow transplantation. Biodistribution studies using iodine 123-labeled anti-CD45 mAb showed uptake in blood, marrow, lymph nodes, spleen, and liver. In a dose-escalation study, 7 dogs treated with the 213Bi-anti-CD45 conjugate (213Bi dose, 0.1-5.9 mCi/kg [3.7-218 MBq/kg]) without marrow grafts had no toxic effects other than a mild, reversible suppression of blood counts. On the basis of these studies, 3 dogs were treated with 0.5 mg/kg 213Bi-labeled anti-CD45 mAb (213Bi doses, 3.6, 4.6, and 8.8 mCi/kg [133, 170, and 326 MBq/kg]) given in 6 injections 3 and 2 days before grafting of marrow from DLA-identical littermates. The dogs also received MMF (10 mg/kg subcutaneously twice daily the day of transplantation until day 27 afterward) and CSP (15 mg/kg orally twice daily the day before transplantation until 35 days afterward). The therapy was well tolerated except for transient elevations in levels of transaminases in 3 dogs, followed by, in one dog, ascites. All dogs had prompt engraftment and achieved stable mixed hematopoietic chimerism, with donor contributions ranging from 30% to 70% after more than 27 weeks of follow-up. These results will form the basis for additional studies in animals and later the design of clinical trials using 213Bi as a nonmyeloablative conditioning regimen with minimal toxicity. © 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: E. R. Nemecek, D. K. Hamlin, D. R. Fisher, K. A. Krohn, J. M. Pagel, F. R. Appelbaum, O. W. Press, and D. C. Matthews Biodistribution of Yttrium-90-Labeled Anti-CD45 Antibody in a Nonhuman Primate Model Clin. Cancer Res., January 15, 2005; 11(2): 787 - 794. [Abstract] [Full Text] [PDF] D. A. Mulford, D. A. Scheinberg, and J. G. Jurcic The Promise of Targeted {alpha}-Particle Therapy J. Nucl. Med., January 1, 2005; 46(1_suppl): 199S - 204S. [Abstract] [Full Text] [PDF] C. E. Muller-Sieburg, R. H. Cho, L. Karlsson, J.-F. Huang, and H. B. Sieburg Myeloid-biased hematopoietic stem cells have extensive self-renewal capacity but generate diminished lymphoid progeny with impaired IL-7 responsiveness Blood, June 1, 2004; 103(11): 4111 - 4118. [Abstract] [Full Text] [PDF] M. A. Caligiuri, A. Velardi, D. A. Scheinberg, and I. M. Borrello Immunotherapeutic Approaches for Hematologic Malignancies Hematology, January 1, 2004; 2004(1): 337 - 353. [Abstract] [Full Text] [PDF] W. A. Bethge, D. S. Wilbur, R. Storb, D. K. Hamlin, E. B. Santos, M. W. Brechbiel, D. R. Fisher, and B. M. Sandmaier Selective T-cell ablation with bismuth-213-labeled anti-TCR{alpha}{beta} as nonmyeloablative conditioning for allogeneic canine marrow transplantation Blood, June 15, 2003; 101(12): 5068 - 5075. [Abstract] [Full Text] [PDF] D. G. Maloney, B. M. Sandmaier, S. Mackinnon, and J. A. Shizuru Non-Myeloablative Transplantation Hematology, January 1, 2002; 2002(1): 392 - 421. [Abstract] [Full Text]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020