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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 (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 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. Social Bookmarking                   What's this? Submitted December 21, 2001 Accepted February 19, 2002 Bismuth-213 labeled anti-CD45 radioimmunoconjugate to condition dogs for nonmyelablative 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 * Corresponding author; email: bsandmai{at}fhcrc.org. To lower treatment related mortality and toxicity of conventional marrow transplantation, a nonmyeloablative regimen was developed using 200 cGy total body irradiation (TBI) and mycophenolate mofetil (MMF) combined with cyclosporine (CSP) as post-grafting immunosuppression. To circumvent potential toxicities of external beam -irradiation, strategies of targeted radiation therapy were investigated. We asked whether the short-lived (t1/2=46 min) -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) without marrow grafts had no toxicity other than mild reversible suppression of blood counts. Based on these studies, 3 dogs were treated with 0.5 mg/kg of 213Bi-labeled anti-CD45 mAb (213Bi doses: 3.6, 4.6 and 8.8 mCi/kg) in 6 injections on days -3 and -2 followed by marrow grafts from DLA-identical littermates and post-grafting MMF (10 mg/kg s.c. b.i.d. days 0-27) and CSP (15 mg/kg b.i.d. p.o. days -1-35). The therapy was well tolerated except for transient elevations of transaminases in three dogs followed by ascites in one. All dogs had prompt engraftment and achieved stable mixed hematopoietic chimerism with donor contributions ranging from 30-70% after >27 weeks follow up. These results will serve as basis for further animal studies and later the design of clinical trials using 213Bi as nonmyeloablative conditioning regimen with minimal toxicity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Nakamae, D. S. Wilbur, D. K. Hamlin, M. S. Thakar, E. B. Santos, D. R. Fisher, A. L. Kenoyer, J. M. Pagel, O. W. Press, R. Storb, et al. Biodistributions, Myelosuppression, and Toxicities in Mice Treated with an Anti-CD45 Antibody Labeled with the {alpha}-Emitting Radionuclides Bismuth-213 or Astatine-211 Cancer Res., March 15, 2009; 69(6): 2408 - 2415. [Abstract] [Full Text] [PDF] C. U. Louis, K. Straathof, C. M. Bollard, C. Gerken, M. H. Huls, M. V. Gresik, M.-F. Wu, H. L. Weiss, A. P. Gee, M. K. Brenner, et al. Enhancing the in vivo expansion of adoptively transferred EBV-specific CTL with lymphodepleting CD45 monoclonal antibodies in NPC patients Blood, March 12, 2009; 113(11): 2442 - 2450. [Abstract] [Full Text] [PDF] P. Kletting, D. Bunjes, S. N. Reske, and G. 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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]

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