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Blood, 1 July 2006, Vol. 108, No. 1, pp. 328-336. Prepublished online as a Blood First Edition Paper on March 23, 2006; DOI 10.1182/blood-2005-11-4327. This Article Full Text (PDF) All Versions of this Article: 2005-11-4327v1 108/1/328    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?  Previous Article  |  Next Article  Submitted November 1, 2005 Accepted February 21, 2006 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 John M Pagel*, Yukang Lin, Nathan Hedin, Anastasia Pantelias, Donald Axworthy, Diane Stone, Don K Hamlin, D S Wilbur, and Oliver W Press Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA Fred Hutchinson Cancer Research Center, Seattle, WA, USA Aletheon Corporation, Seattle, WA, USA Department of Radiation Oncology, University of Washington, Seattle, WA, USA Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA; Department of Biological Structure, University of Washington, Seattle, WA, USA * Corresponding author; email: jpagel{at}fhcrc.org. The efficacy of radioimmunotherapy (RIT) for patients with relapsed non-Hodgkin's lymphoma (NHL) is limited by non-specific delivery of radiation to normal tissues due to the long circulating half-life of radiolabeled anti-CD20 antibodies (Ab). Pretargeted RIT using a covalent conjugate of the 1F5 anti-CD20 Ab with streptavidin (SA) has been shown to augment the efficacy of RIT and decrease toxicity compared with a directly labeled 1F5 Ab. We have engineered a tetravalent single-chain 1F5 (scFv)4SA fusion protein and compared it to the 1F5-SA conjugate. Athymic mice bearing Ramos lymphoma xenografts received either the conjugate or fusion protein, followed 20 hours later by a biotin-N-acetyl-galactosamine clearing agent, followed 4 hours later by 111In-DOTA-biotin. After 24 hours, 11.4 ± 2.1% of the injected dose of radionuclide was present per gram of tumor (% ID/g) using 1F5 (scFv)4SA compared with 10.8 ± 2.5% ID/g with 1F5 Ab-SA. Superior tumor-to-normal organ ratios of radioactivity were consistently seen using the fusion protein compared to the chemical conjugate (e.g., tumor-to-blood ratio >65:1 after 48 hours with the fusion protein, but < 7:1 with the conjugate). More than 90% of lymphoma-bearing mice could be cured with minimal toxicity using either reagent followed by 1200 µCi of 90Y-DOTA-biotin. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. J. Green, J. M. Pagel, E. R. Nemecek, Y. Lin, A. Kenoyer, A. Pantelias, D. K. Hamlin, D. S. Wilbur, D. R. Fisher, J. G. Rajendran, et al. Pretargeting CD45 enhances the selective delivery of radiation to hematolymphoid tissues in nonhuman primates Blood, August 6, 2009; 114(6): 1226 - 1235. [Abstract] [Full Text] [PDF] J. M. Pagel, N. Orgun, D. K. Hamlin, D. S. Wilbur, T. A. Gooley, A. K. Gopal, S. I. Park, D. J. Green, Y. Lin, and O. W. Press A comparative analysis of conventional and pretargeted radioimmunotherapy of B-cell lymphomas by targeting CD20, CD22, and HLA-DR singly and in combinations Blood, May 14, 2009; 113(20): 4903 - 4913. [Abstract] [Full Text] [PDF] R. M. Sharkey, H. Karacay, S. Litwin, E. A. Rossi, W. J. McBride, C.-H. Chang, and D. M. Goldenberg Improved Therapeutic Results by Pretargeted Radioimmunotherapy of Non-Hodgkin's Lymphoma with a New Recombinant, Trivalent, Anti-CD20, Bispecific Antibody Cancer Res., July 1, 2008; 68(13): 5282 - 5290. [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]

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