This Article 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 Saga, T. Articles by Neumann, R. D. Search for Related Content PubMed PubMed Citation Articles by Saga, T. Articles by Neumann, R. D.

Two-Step Targeting of Experimental Lung Metastases with Biotinylated Antibody and Radiolabeled Streptavidin

Nuclear Medicine Department, Clinical Center [T. S., R. D. N., J. M. J., J. T. L., N. L., C. H. P.]; Laboratory of Molecular Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute [T. H., J. N. W.]; and Biomedical Engineering and Instrumentation Program [C. S.], National Center for Research Resources, NIH, Bethesda, Maryland 20892

Two-step monoclonal antibody tumor targeting using an avidin-biotin system has unique characteristics because of the high-affinity binding (10¹⁵ M^-1) and the lower molecular weight ligands (avidin, streptavidin, or biotin) used as carriers of radioisotopes, toxins, or drugs. The distribution of radiolabeled streptavidin in a two-step targeting strategy was investigated in lung metastases of line 10 carcinoma in guinea plgs. The micro-distribution of administered D3 monoclonal antibody and ¹²⁵I-labeled streptavidin in metastatic nodules was examined by immunohistochemistry and autoradiography, and the uptake was quantitated. With monoclonal antibody pretargeting, streptavidin was found mainly at the periphery of metastatic nodules 1.5 h after injection; it had penetrated deeper at 4 h and was approaching homogeneity in many of the tumor nodules at 24 h. These results indicate that streptavidin can penetrate into metastatic nodules more rapidly than can the antibody. The concentration of streptavidin in metastatic nodules 4 h after injection was 5.6 times higher for the pretargeted group than for the nonpretargeted group, and the pretargeting index was 4.7. Although the absolute uptake of streptavidin had decreased between 4 and 24 h, the metastasis:blood ratio had increased from 1.2 to 2.4. When compared with the animals injected with ¹²⁵I-labeled D3 antibody alone, the pretargeted group achieved higher tumor:blood and tumor:lung ratios and a higher localization index at early times after injection of the radiolabeled species.

¹ Present address: Kurashiki Central Hospital, Kurashiki 710, Japan.

² Present address: Takeda, Inc., Yodogawa-ku, Osaka 532, Japan.

³ To whom reprint requests should be addressed, at Nuclear Medicine Department, Clinical Center, Building 10, Room 1C-496, NIH, 9000 Rockville Pike, Bethesda, MD 20892.

Received 10/19/93. Accepted 2/17/94.

This article has been cited by other articles:

				L. Martensson, R. Nilsson, T. Ohlsson, H.-O. Sjogren, S.-E. Strand, and J. Tennvall Improved Tumor Targeting and Decreased Normal Tissue Accumulation through Extracorporeal Affinity Adsorption in a Two-Step Pretargeting Strategy Clin. Cancer Res., September 15, 2007; 13(18): 5572s - 5576s. [Abstract] [Full Text] [PDF]

				D. M. Goldenberg, R. M. Sharkey, G. Paganelli, J. Barbet, and J.-F. Chatal Antibody Pretargeting Advances Cancer Radioimmunodetection and Radioimmunotherapy J. Clin. Oncol., February 10, 2006; 24(5): 823 - 834. [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]

				A. Forero, P. L. Weiden, J. M. Vose, S. J. Knox, A. F. LoBuglio, J. Hankins, M. L. Goris, V. J. Picozzi, D. B. Axworthy, H. B. Breitz, et al. Phase 1 trial of a novel anti-CD20 fusion protein in pretargeted radioimmunotherapy for B-cell non-Hodgkin lymphoma Blood, July 1, 2004; 104(1): 227 - 236. [Abstract] [Full Text] [PDF]

				M. R. Lewis, M. Wang, D. B. Axworthy, L. J. Theodore, R. W. Mallet, A. R. Fritzberg, M. J. Welch, and C. J. Anderson In Vivo Evaluation of Pretargeted 64Cu for Tumor Imaging and Therapy J. Nucl. Med., August 1, 2003; 44(8): 1284 - 1292. [Abstract] [Full Text] [PDF]

				J. M. Pagel, N. Hedin, K. Subbiah, D. Meyer, R. Mallet, D. Axworthy, L. J. Theodore, D. S. Wilbur, D. C. Matthews, and O. W. Press Comparison of anti-CD20 and anti-CD45 antibodies for conventional and pretargeted radioimmunotherapy of B-cell lymphomas Blood, March 15, 2003; 101(6): 2340 - 2348. [Abstract] [Full Text] [PDF]

				S. Ponnazhagan, G. Mahendra, S. Kumar, J. A. Thompson, and M. Castillas Jr. Conjugate-Based Targeting of Recombinant Adeno-Associated Virus Type 2 Vectors by Using Avidin-Linked Ligands J. Virol., November 13, 2002; 76(24): 12900 - 12907. [Abstract] [Full Text] [PDF]

				C.-H. Chang, R. M. Sharkey, E. A. Rossi, H. Karacay, W. McBride, H. J. Hansen, J.-F. Chatal, J. Barbet, and D. M. Goldenberg Molecular Advances in Pretargeting Radioimunotherapy with Bispecific Antibodies Mol. Cancer Ther., May 1, 2002; 1(7): 553 - 563. [Abstract] [Full Text] [PDF]

				O. W. Press, M. Corcoran, K. Subbiah, D. K. Hamlin, D. S. Wilbur, T. Johnson, L. Theodore, E. Yau, R. Mallett, D. L. Meyer, et al. A comparative evaluation of conventional and pretargeted radioimmunotherapy of CD20-expressing lymphoma xenografts Blood, October 15, 2001; 98(8): 2535 - 2543. [Abstract] [Full Text] [PDF]

				M. Moro, A. M. Gasparri, S. Pagano, M. Bellone, P. Tornaghi, F. Veglia, A. Corti, G. Casorati, and P. Dellabona Induction of Therapeutic T-Cell Immunity by Tumor Targeting with Soluble Recombinant B7-Immunoglobulin Costimulatory Molecules Cancer Res., June 1, 1999; 59(11): 2650 - 2656. [Abstract] [Full Text] [PDF]

				A. Gasparri, M. Moro, F. Curnis, A. Sacchi, S. Pagano, F. Veglia, G. Casorati, A. G. Siccardi, P. Dellabona, and A. Corti Tumor Pretargeting with Avidin Improves the Therapeutic Index of Biotinylated Tumor Necrosis Factor {{alpha}} in Mouse Models Cancer Res., June 1, 1999; 59(12): 2917 - 2923. [Abstract] [Full Text] [PDF]