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Prepublished online as a Blood First Edition Paper on November 21, 2002; DOI 10.1182/blood-2002-03-0874. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-03-0874v1 101/6/2340    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 Pagel, J. M. Articles by Press, O. W. Search for Related Content PubMed PubMed Citation Articles by Pagel, J. M. Articles by Press, O. W. Related Collections Immunotherapy Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 March 2003, Vol. 101, No. 6, pp. 2340-2348 NEOPLASIA Comparison of anti-CD20 and anti-CD45 antibodies for conventional and pretargeted radioimmunotherapy of B-cell lymphomas John M. Pagel, Nathan Hedin, Krishnan Subbiah, Damon Meyer, Robert Mallet, Donald Axworthy, Louis J. Theodore, D. Scott Wilbur, Dana C. Matthews, and Oliver W. Press From the Fred Hutchinson Cancer Research Center and the Departments of Medicine, Radiation Oncology, Pediatrics, and Biological Structure, University of Washington, Seattle; and NeoRx Corporation, Seattle, WA. Radiolabeled anti-CD20 antibodies produce responses in 60% to 95% of patients with relapsed non-Hodgkin lymphoma (NHL); however, absorbed radiation ratios between tumors and normal organs are relatively low, and many patients have relapses. In this study we compared the abilities of anti-CD45 (BC8) and anti-CD20 (1F5) antibodies to target human Ramos lymphoma xenografts in athymic mice. When direct radioiodination was performed with conventional methods, BC8 delivered 2- to 4-fold more radioiodine to tumors than 1F5, with tumor-to-normal organ ratios as high as 20:1 using radiolabeled BC8 compared with a maximal ratio of 9.8:1 using radioiodinated 1F5. To optimize the biodistribution of radioactivity, we performed studies following a pretargeting method using streptavidin (SA)-conjugated BC8 and 1F5. Injection of a synthetic clearing agent decreased the circulating level of conjugates by 80% to 90% within 1 hour. Pretargeting with BC8-SA resulted in a 2- to 4-fold greater tumor uptake of radiolabeled biotin than with 1F5-SA, with maximal tumor-to-normal organ ratios of more than 80:1 and approximately 16:1, respectively. Therapy experiments demonstrated that 400 µCi (14.8 MBq) or more of yttrium-90-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin cured 100% of mice treated with BC8-SA and more than 90% of mice pretargeted with 1F5-SA, with complete remission occurring 8 to 10 days sooner in mice receiving BC8-SA. After treatment with 200 µCi (7.4 MBq) 90Y-DOTA-biotin, 70% of the mice treated with BC8-SA were cured, but no mice were cured using 1F5-SA. Doses up to 800 µCi (29.6 MBq) 90Y-DOTA-biotin were delivered with minor toxicity using either antibody conjugate. These lymphoma xenograft data suggest that pretargeted radioimmunotherapy using either anti-CD20 or anti-CD45 conjugates is highly effective and minimally toxic. © 2003 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: G. Liu, S. Dou, M. Rusckowski, and D. J. Hnatowich An experimental and theoretical evaluation of the influence of pretargeting antibody on the tumor accumulation of effector Mol. Cancer Ther., May 1, 2008; 7(5): 1025 - 1032. [Abstract] [Full Text] [PDF] R. B. Walter, K. M. Boyle, F. R. Appelbaum, I. D. Bernstein, and J. M. Pagel Simultaneously targeting CD45 significantly increases cytotoxicity of the anti-CD33 immunoconjugate, gemtuzumab ozogamicin, against acute myeloid leukemia (AML) cells and improves survival of mice bearing human AML xenografts Blood, May 1, 2008; 111(9): 4813 - 4816. [Abstract] [Full Text] [PDF] J. M. Pagel, N. Hedin, L. Drouet, B. L. Wood, A. Pantelias, Y. Lin, D. K. Hamlin, D. S. Wilbur, A. K. Gopal, D. Green, et al. Eradication of disseminated leukemia in a syngeneic murine leukemia model using pretargeted anti-CD45 radioimmunotherapy Blood, February 15, 2008; 111(4): 2261 - 2268. [Abstract] [Full Text] [PDF] D. J. Green, J. M. Pagel, A. Pantelias, N. Hedin, Y. Lin, D. S. Wilbur, A. Gopal, D. K. Hamlin, and O. W. Press Pretargeted Radioimmunotherapy for B-Cell Lymphomas Clin. Cancer Res., September 15, 2007; 13(18): 5598s - 5603s. [Abstract] [Full Text] [PDF] J. M. Pagel, A. Pantelias, N. Hedin, S. Wilbur, L. Saganic, Y. Lin, D. Axworthy, D. K. Hamlin, D. S. Wilbur, A. K. Gopal, et al. Evaluation of CD20, CD22, and HLA-DR Targeting for Radioimmunotherapy of B-Cell Lymphomas Cancer Res., June 15, 2007; 67(12): 5921 - 5928. [Abstract] [Full Text] [PDF] A. Pantelias, J. M. Pagel, N. Hedin, L. Saganic, S. Wilbur, D. K. Hamlin, D. S. Wilbur, Y. Lin, D. Stone, D. Axworthy, et al. Comparative biodistributions of pretargeted radioimmunoconjugates targeting CD20, CD22, and DR molecules on human B-cell lymphomas Blood, June 1, 2007; 109(11): 4980 - 4987. [Abstract] [Full Text] [PDF] F. Baron, R. Storb, B. E. Storer, M. B. Maris, D. Niederwieser, J. A. Shizuru, T. R. Chauncey, B. Bruno, S. J. Forman, P. A. McSweeney, et al. Factors Associated With Outcomes in Allogeneic Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning After Failed Myeloablative Hematopoietic Cell Transplantation J. Clin. Oncol., September 1, 2006; 24(25): 4150 - 4157. [Abstract] [Full Text] [PDF] J. M. Pagel, Y. Lin, N. Hedin, A. Pantelias, D. Axworthy, D. Stone, D. K. Hamlin, D. S. Wilbur, and O. W. Press Comparison of a tetravalent single-chain antibody-streptavidin fusion protein and an antibody-streptavidin chemical conjugate for pretargeted anti-CD20 radioimmunotherapy of B-cell lymphomas Blood, July 1, 2006; 108(1): 328 - 336. [Abstract] [Full Text] [PDF] Y. Lin, J. M. Pagel, D. Axworthy, A. Pantelias, N. Hedin, and O. W. Press A Genetically Engineered Anti-CD45 Single-Chain Antibody-Streptavidin Fusion Protein for Pretargeted Radioimmunotherapy of Hematologic Malignancies. Cancer Res., April 1, 2006; 66(7): 3884 - 3892. [Abstract] [Full Text] [PDF] N. Sato, R. Hassan, D. B. Axworthy, K. J. Wong, S. Yu, L. J. Theodore, Y. Lin, L. Park, M. W. Brechbiel, I. Pastan, et al. Pretargeted Radioimmunotherapy of Mesothelin-Expressing Cancer Using a Tetravalent Single-Chain Fv-Streptavidin Fusion Protein J. Nucl. Med., July 1, 2005; 46(7): 1201 - 1209. [Abstract] [Full Text] [PDF] 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]

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