This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yao, Z. Articles by Carrasquillo, J. A. Search for Related Content PubMed PubMed Citation Articles by Yao, Z. Articles by Carrasquillo, J. A.

Radioimmunotherapy of A431 Xenografted Mice with Pretargeted B3 Antibody-Streptavidin and ⁹⁰Y-labeled 1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic Acid (DOTA)-Biotin

Nuclear Medicine Department of the Warren G. Magnuson Clinical Center [Z. Y., K. J. W., L. P., C. W. P., C. H. P., J. A. C.], Metabolism Branch [M. Z., T. A. W.], Radiation Oncology Branch [K. G., M. W. B.], and Laboratory of Molecular Biology [I. P.], National Cancer Institute, NIH, Bethesda, Maryland 20892, and NeoRx Corporation, Seattle, Washington 98119 [D. B. A., R. W. M., L. J. T., E. K. Y.]

We investigated the biodistribution of ⁸⁸Y/¹¹¹In-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-biotin and therapy with ⁹⁰Y-labeled DOTA-biotin in tumor-bearing mice after B3-streptavidin antibody conjugate (B3-SA) pretargeting. B3 antibody, recognizing Lewis^y antigen, was conjugated to streptavidin (B3-SA). For pretargeting, 400 µg of the B3-SA was injected i.v. into mice bearing A431 tumor xenografts. After tumor localization of B3-SA, 100 µg of synthetic clearing agent was injected i.v. to clear the unbound B3-SA from the circulation. Four h later, 1 µg of radiolabeled DOTA-biotin was injected i.v. Radioimmunotherapy was performed with doses of 9.25 to 37 MBq of ⁹⁰Y-labeled DOTA-biotin. As a result, radiolabeled DOTA-biotin cleared rapidly. All of the normal tissues had <2.6% of the injected dose per gram, whereas tumor uptake reached 15% ID/g. The total tumor uptake of radioactivity remained similar for 96 h or longer. In the first study, the median survival of the control group was 8 days, whereas it increased to >163 days in the 37 MBq ⁹⁰Y group (P < 0.005). In a second therapy group, 7 of 10 mice receiving 37 MBq of ⁹⁰Y and B3-SA were cured, and remained healthy for >180 days after therapy, compared with control groups, with 29.2 days mean survival time (P < 0.001). Tumor pretargeting with B3-SA and radiolabeled DOTA-biotin has shown favorable, specific, and fast targeting that has resulted in good tumor responses and, thus, serves as a rationale for human studies with the B3-SA pretargeting approach.

This article has been cited by other articles:

				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]

				A. Khaibullina, B.-S. Jang, H. Sun, N. Le, S. Yu, V. Frenkel, J. A. Carrasquillo, I. Pastan, K. C.P. Li, and C. H. Paik Pulsed High-Intensity Focused Ultrasound Enhances Uptake of Radiolabeled Monoclonal Antibody to Human Epidermoid Tumor in Nude Mice J. Nucl. Med., February 1, 2008; 49(2): 295 - 302. [Abstract] [Full Text] [PDF]

				M. Zhang, Z. Yao, H. Patel, K. Garmestani, Z. Zhang, V. S. Talanov, P. S. Plascjak, C. K. Goldman, J. E. Janik, M. W. Brechbiel, et al. Effective therapy of murine models of human leukemia and lymphoma with radiolabeled anti-CD30 antibody, HeFi-1 PNAS, May 15, 2007; 104(20): 8444 - 8448. [Abstract] [Full Text] [PDF]

				D. Moosmayer, D. Berndorff, C.-H. Chang, R. M. Sharkey, A. Rother, S. Borkowski, E. A. Rossi, W. J. McBride, T. M. Cardillo, D. M. Goldenberg, et al. Bispecific antibody pretargeting of tumor neovasculature for improved systemic radiotherapy of solid tumors. Clin. Cancer Res., September 15, 2006; 12(18): 5587 - 5595. [Abstract] [Full Text] [PDF]

				G. Liu, S. Dou, G. Mardirossian, J. He, S. Zhang, X. Liu, M. Rusckowski, and D. J. Hnatowich Successful Radiotherapy of Tumor in Pretargeted Mice by 188Re-Radiolabeled Phosphorodiamidate Morpholino Oligomer, a Synthetic DNA Analogue. Clin. Cancer Res., August 15, 2006; 12(16): 4958 - 4964. [Abstract] [Full Text] [PDF]

				J. M. Pagel, Y. Lin, N. Hedin, A. Pantelias, D. Axworthy, D. Stone, D. K. Hamlin, D. S. Wilbur, and O. W. Press 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 Blood, July 1, 2006; 108(1): 328 - 336. [Abstract] [Full Text] [PDF]

				M. P. Kelly, F. T. Lee, F. E. Smyth, M. W. Brechbiel, and A. M. Scott Enhanced Efficacy of 90Y-Radiolabeled Anti-Lewis Y Humanized Monoclonal Antibody hu3S193 and Paclitaxel Combined-Modality Radioimmunotherapy in a Breast Cancer Model J. Nucl. Med., April 1, 2006; 47(4): 716 - 725. [Abstract] [Full Text] [PDF]

				Y. Lin, J. M. Pagel, D. Axworthy, A. Pantelias, N. Hedin, and O. W. Press A Genetically Engineered Anti-CD45 Single-Chain Antibody-Streptavidin Fusion Protein for Pretargeted Radioimmunotherapy of Hematologic Malignancies. Cancer Res., April 1, 2006; 66(7): 3884 - 3892. [Abstract] [Full Text] [PDF]

				G. J. Forster, E. B. Santos, P. M. Smith-Jones, P. Zanzonico, and S. M. Larson Pretargeted Radioimmunotherapy with a Single-Chain Antibody/Streptavidin Construct and Radiolabeled DOTA-Biotin: Strategies for Reduction of the Renal Dose J. Nucl. Med., January 1, 2006; 47(1): 140 - 149. [Abstract] [Full Text] [PDF]

				D. J. Buchsbaum, M.B. Khazaeli, D. B. Axworthy, J. Schultz, T. R. Chaudhuri, K. R. Zinn, M. Carpenter, and A. F. LoBuglio Intraperitoneal Pretarget Radioimmunotherapy with CC49 Fusion Protein Clin. Cancer Res., November 15, 2005; 11(22): 8180 - 8185. [Abstract] [Full Text] [PDF]

				H. Karacay, P.-Y. Brard, R. M. Sharkey, C.-H. Chang, E. A. Rossi, W. J. McBride, D. R. Ragland, I. D. Horak, and D. M. Goldenberg Therapeutic Advantage of Pretargeted Radioimmunotherapy Using a Recombinant Bispecific Antibody in a Human Colon Cancer Xenograft Clin. Cancer Res., November 1, 2005; 11(21): 7879 - 7885. [Abstract] [Full Text] [PDF]

				N. Sato, R. Hassan, D. B. Axworthy, K. J. Wong, S. Yu, L. J. Theodore, Y. Lin, L. Park, M. W. Brechbiel, I. Pastan, et al. Pretargeted Radioimmunotherapy of Mesothelin-Expressing Cancer Using a Tetravalent Single-Chain Fv-Streptavidin Fusion Protein J. Nucl. Med., July 1, 2005; 46(7): 1201 - 1209. [Abstract] [Full Text] [PDF]

				R. M. Sharkey The Direct Route May Not Be the Best Way to Home J. Nucl. Med., March 1, 2005; 46(3): 391 - 394. [Full Text] [PDF]

				R. M. Sharkey and D. M. Goldenberg Perspectives on Cancer Therapy with Radiolabeled Monoclonal Antibodies J. Nucl. Med., January 1, 2005; 46(1_suppl): 115S - 127S. [Abstract] [Full Text] [PDF]

				Z. Yao, M. Zhang, K. Garmestani, D. B. Axworthy, R. W. Mallett, A. R. Fritzberg, L. J. Theodore, P. S. Plascjak, W. C. Eckelman, T. A. Waldmann, et al. Pretargeted {alpha} Emitting Radioimmunotherapy Using 213Bi 1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-Tetraacetic Acid-Biotin Clin. Cancer Res., May 1, 2004; 10(9): 3137 - 3146. [Abstract] [Full Text] [PDF]

				M. Zhang, Z. Zhang, K. Garmestani, J. Schultz, D. B. Axworthy, C. K. Goldman, M. W. Brechbiel, J. A. Carrasquillo, and T. A. Waldmann Pretarget radiotherapy with an anti-CD25 antibody-streptavidin fusion protein was effective in therapy of leukemia/lymphoma xenografts PNAS, February 18, 2003; 100(4): 1891 - 1895. [Abstract] [Full Text] [PDF]