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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 (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 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 Social Bookmarking                   What's this? Submitted March 20, 2002 Accepted October 20, 2002 A 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 Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Department of Medicine, University of Washington, Seattle, WA, USA Department of Radiation Oncology, University of Washington, Seattle, WA, USA Department of Pediatrics, University of Washington, Seattle, WA, USA Department of Biological Structure, University of Washington, Seattle, WA, USA NeoRx Corporation, Seattle, WA, USA * Corresponding author; email: jpagel{at}fhcrc.org. Radiolabeled anti-CD20 antibodies produce responses in 60-95% of relapsed non-Hodgkin's lymphoma (NHL) patients; however, tumor-to-normal organ ratios of absorbed radiation are relatively low and many patients relapse. 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 2-4 fold more radioiodine to tumors than 1F5, with tumor-to-normal organ ratios of up to 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 using a pretargeting method employing streptavidin (SA)-conjugated BC8 and 1F5. Injection of a synthetic clearing agent decreased the circulating level of conjugates by 80-90% within 1 hour. Pretargeting with BC8-SA resulted in a 2-4 fold greater tumor uptake of radiolabeled biotin compared to 1F5-SA, with maximal tumor-to-normal organ ratios of >80:1 and ~16:1, respectively. Therapy experiments demonstrated that 400 µCi of 90Y-DOTA-biotin cured 100% of mice treated with BC8-SA and >90% of mice pretargeted with 1F5-SA, with complete remissions occurring 8-10 days sooner in mice receiving BC8-SA. After treatment with 200 µCi of 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 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. K. Gopal, J. M. Pagel, J. R. Fromm, S. Wilbur, and O. 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