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Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2002-01-0107. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-01-0107v1 100/1/208    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 Zhang, M. Articles by Waldmann, T. A. Search for Related Content PubMed PubMed Citation Articles by Zhang, M. Articles by Waldmann, T. A. Related Collections Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2002, Vol. 100, No. 1, pp. 208-216 NEOPLASIA Pretargeting radioimmunotherapy of a murine model of adult T-cell leukemia with the -emitting radionuclide, bismuth 213 Meili Zhang, Zhengsheng Yao, Kayhan Garmestani, Donald B. Axworthy, Zhuo Zhang, Robert W. Mallett, Louis J. Theodore, Carolyn K. Goldman, Martin W. Brechbiel, Jorge A. Carrasquillo, and Thomas A. Waldmann From the Metabolism Branch, Center for Cancer Research, National Cancer Institute; Nuclear Medicine Department, Clinical Center; Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; and NeoRx Corporation, Seattle, WA. We used a pretargeting technique to treat a nonobese diabetic/severe combined immunodeficient murine model of human adult T-cell leukemia with an anti-Tac antibody-streptavidin (HAT-SA) conjugate, which recognizes CD25, followed by bismuth 213 (213Bi)-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)- biotin. In the 3-step pretargeting radioimmunotherapy protocol, HAT-SA (140 or 400 µg) was administered intravenously (i.v.) to bind to the interleukin 2 receptor  (IL-2R; CD25)-expressing tumor cells. After 24 hours, 100 µg of a synthetic clearing agent was administered i.v. to remove unbound circulating HAT-SA conjugate from the circulation. Four hours later, 213Bi-DOTA-biotin was administered i.v. for therapy. Tumor growth was significantly inhibited in 3 trials by using 250 µCi (9.25 MBq) of 213Bi-DOTA-biotin with a pretargeting technique as monitored by serum levels of soluble IL-2R and/or human -2-microglobulin (P < .05, t test) and by survival of tumor-bearing mice in the treatment groups (P < .02, log rank test) as compared with the control groups. No prolongation of survival was observed with a nonspecific antibody-SA conjugate or in the absence of the radionuclide. Additionally, no prolongation of survival resulted from administration of 213Bi directly linked to intact HAT. Furthermore, there was no prolongation of survival when the -emitting radionuclide yttrium 90 instead of the -emitting radionuclide 213Bi was used. The pretargeting approach with 213Bi inhibited tumor growth more effectively than did immunotherapy with unmodified HAT. The best results were obtained with combination therapy that involved 213Bi-DOTA-biotin with a pretargeting technique supplemented by 4 weekly doses of HAT. The findings of this study support the use of this combination approach in a clinical trial in patients with IL-2R-expressing leukemias. © 2002 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: 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. Chen, M. Zhang, W. Ju, and T. A. 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	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020