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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4980-4987. Prepublished online as a Blood First Edition Paper on February 15, 2007; DOI 10.1182/blood-2006-11-056895. This Article Full Text (PDF) All Versions of this Article: blood-2006-11-056895v1 109/11/4980    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 Pantelias, A. Articles by Press, O. W Search for Related Content PubMed PubMed Citation Articles by Pantelias, A. Articles by Press, O. W Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 9, 2006 Accepted January 30, 2007 Comparative biodistributions of pretargeted radioimmunoconjugates targeting CD20, CD22 and DR molecules on human B cell lymphomas Anastasia Pantelias, John M. Pagel*, Nathan Hedin, Laura Saganic, Shani Wilbur, Donald K Hamlin, D. Scott Wilbur, Yukang Lin, Diane Stone, Don Axworthy, Ajay K Gopal, and Oliver W Press Fred Hutchinson Cancer Research Center, Seattle, WA, United States Department of Radiation Oncology, University of Washington, Seattle, WA, United States Aletheon Pharmaceuticals, Inc., Seattle, WA, United States Division of Oncology of the University of Washington School of Medicine, Seattle, WA, United States Department of Biological Structure, University of Washington, Seattle, WA, United States * Corresponding author; email: jpagel{at}fhcrc.org. Pretargeted radioimmunotherapy (PRIT) using streptavidin (SA) conjugated antibodies (Ab), followed by clearing agent and radiolabeled biotin is a promising method that can increase the effectiveness of RIT, while decreasing the toxicities associated with directly labeled Abs. Although CD20 has been the traditional target antigen for RIT of non-Hodgkin's lymphoma (NHL), studies targeting HLA DR and CD22 have yielded promising results. Targeting all three antigens at once may further augment the effect of PRIT. This study compares the targeting of Ramos, Raji and FL-18 lymphoma xenografts with either anti-CD20 Ab/SA (1F5/SA), anti-HLA DR Ab/SA (Lym-1/SA), anti-CD22 Ab/SA (HD39/SA) or all three conjugates in combination, followed 24 hours later by a biotin-N-acetyl-galactosamine clearing agent, and 3 hours after that by 111In-DOTA-biotin. The Ab/SA conjugate yielding the best tumor uptake and tumor-to-normal organ ratios of radioactivity varied depending on the target antigen expression on the cell line employed, with 1F5/SA and Lym-1/SA yielding the most promising results overall. Also, the best tumor-to-normal organ ratios of absorbed radioactivity were obtained using single conjugates optimized for target tumor antigen expression rather than the combination therapy. This study highlights the importance of screening the antigenic expression on lymphomas to select the optimal reagent for PRIT. 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] D. V. Gold, D. M. Goldenberg, H. Karacay, E. A. Rossi, C.-H. Chang, T. M. Cardillo, W. J. McBride, and R. M. Sharkey A Novel Bispecific, Trivalent Antibody Construct for Targeting Pancreatic Carcinoma Cancer Res., June 15, 2008; 68(12): 4819 - 4826. [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]

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