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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 (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 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 Social Bookmarking                   What's this? Submitted January 15, 2002 Accepted February 15, 2002 Pretargeting radioimmunotherapy of a murine model of adult T cell leukemia (ATL) with the alpha emitting radionuclide, Bi-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* * Corresponding author; email: tawald{at}helix.nih.gov. We used a pretargeting technique to treat a SCID/NOD murine model of human adult T-cell leukemia (ATL) with an anti-Tac antibody-streptavidin conjugate (HAT-SA), which recognizes CD25, followed by 213Bi-DOTA-biotin. In the three-step pretargeting radioimmunotherapy protocol, HAT-SA (140 or 400 µg) was administered intravenously (i.v.) to bind to the 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 three trials using 250 µCi of 213Bi-DOTA-biotin with a pretargeting technique as monitored by serum levels of sIL-2R and/or human ß2 microglobulin (p<0.05, t-test) and by survival of tumor bearing mice in the treatment groups (p<0.02, rank test) as compared with the control groups. No prolongation of survival was observed with a non-specific 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 ß-emitting radionuclide 90Y 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 four 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. 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. Waldmann Effective treatment of a murine model of adult T-cell leukemia using depsipeptide and its combination with unmodified daclizumab directed toward CD25 Blood, February 5, 2009; 113(6): 1287 - 1293. 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