Originally published as JCO Early Release 10.1200/JCO.2005.03.8471 on December 27 2005

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goldenberg, D. M. Articles by Chatal, J.-F. Search for Related Content PubMed PubMed Citation Articles by Goldenberg, D. M. Articles by Chatal, J.-F. Social Bookmarking                            What's this?

Antibody Pretargeting Advances Cancer Radioimmunodetection and Radioimmunotherapy

From the Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ; Department of Nuclear Medicine, European Institute of Oncology, Milan, Italy; and Department of Nuclear Medicine, Institut Régional du Cancer and Institut National de la Santé et de la Recherche Médicale, Nantes, France

Address reprint requests to David M. Goldenberg, ScD, MD, Garden State Cancer Center, CMMI, 520 Belleville Avenue, Belleville, NJ 07109; e-mail: dmg.gscancer{at}att.net

This article reviews the methods of pretargeting, which involve separating the targeting antibody from the subsequent delivery of an imaging or therapeutic agent that binds to the tumor-localized antibody. This provides enhanced tumor:background ratios and the delivery of a higher therapeutic dose than when antibodies are directly conjugated with radionuclides, as currently practiced in cancer radioimmunotherapy. We describe initial promising clinical results using streptavidin-antibody constructs with biotin-radionuclide conjugates in the treatment of patients with malignant gliomas, and of bispecific antibodies with hapten-radionuclides in the therapy of tumors expressing carcinoembryonic antigen, such as medullary thyroid and small-cell lung cancers.

Supported in part by US Public Health Service Grant No. PO1 CA103985 from the National Cancer Institute (National Institutes of Health [NIH], Bethesda, MD); Office of Science, US Department of Energy Grant No. DE-FG02-95ER62028 and USPHS Grant No. EB002114 from the National Institute of Biomedical Imaging and Bioengineering, NIH; and Grant No. 05-1842-FS-N-0 from the New Jersey Department of Health and Senior Services; Italian Association for Cancer Research; and by grants from the French Ministry of Health (Programmes Hospitaliers de Recherche Clinique 1999 and 2002).

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				W. J. McBride, R. M. Sharkey, H. Karacay, C. A. D'Souza, E. A. Rossi, P. Laverman, C.-H. Chang, O. C. Boerman, and D. M. Goldenberg A Novel Method of 18F Radiolabeling for PET J. Nucl. Med., June 1, 2009; 50(6): 991 - 998. [Abstract] [Full Text] [PDF]

				D. M. Goldenberg Some like it hot: lymphoma radioimmunotherapy Blood, May 14, 2009; 113(20): 4823 - 4824. [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]

				R. M. Sharkey, H. Karacay, C. R. Johnson, S. Litwin, E. A. Rossi, W. J. McBride, C.-H. Chang, and D. M. Goldenberg Pretargeted Versus Directly Targeted Radioimmunotherapy Combined with Anti-CD20 Antibody Consolidation Therapy of Non-Hodgkin Lymphoma J. Nucl. Med., March 1, 2009; 50(3): 444 - 453. [Abstract] [Full Text] [PDF]

				P. Kletting, D. Bunjes, S. N. Reske, and G. Glatting Improving Anti-CD45 Antibody Radioimmunotherapy Using a Physiologically Based Pharmacokinetic Model J. Nucl. Med., February 1, 2009; 50(2): 296 - 302. [Abstract] [Full Text] [PDF]

				J. M. Pagel, D. C. Matthews, A. Kenoyer, D. K. Hamlin, D. S. Wilbur, D. R. Fisher, A. K. Gopal, Y. Lin, L. Saganic, F. R. Appelbaum, et al. Pretargeted Radioimmunotherapy Using Anti-CD45 Monoclonal Antibodies to Deliver Radiation to Murine Hematolymphoid Tissues and Human Myeloid Leukemia Cancer Res., January 1, 2009; 69(1): 185 - 192. [Abstract] [Full Text] [PDF]

				X. Zhou, W. Hu, and X. Qin The Role of Complement in the Mechanism of Action of Rituximab for B-Cell Lymphoma: Implications for Therapy Oncologist, September 1, 2008; 13(9): 954 - 966. [Abstract] [Full Text] [PDF]

				R. M. Sharkey, H. Karacay, S. Litwin, E. A. Rossi, W. J. McBride, C.-H. Chang, and D. M. Goldenberg Improved Therapeutic Results by Pretargeted Radioimmunotherapy of Non-Hodgkin's Lymphoma with a New Recombinant, Trivalent, Anti-CD20, Bispecific Antibody Cancer Res., July 1, 2008; 68(13): 5282 - 5290. [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]

				M. Ychou, D. Azria, C. Menkarios, P. Faurous, F. Quenet, B. Saint-Aubert, P. Rouanet, M. Pelegrin, C. Bascoul-Mollevi, D. Guerreau, et al. Adjuvant Radioimmunotherapy Trial with Iodine-131-Labeled Anti-Carcinoembryonic Antigen Monoclonal Antibody F6 F(ab')2 after Resection of Liver Metastases from Colorectal Cancer Clin. Cancer Res., June 1, 2008; 14(11): 3487 - 3493. [Abstract] [Full Text] [PDF]

				G. M. Thurber and K. D. Wittrup Quantitative Spatiotemporal Analysis of Antibody Fragment Diffusion and Endocytic Consumption in Tumor Spheroids Cancer Res., May 1, 2008; 68(9): 3334 - 3341. [Abstract] [Full Text] [PDF]

				G. Liu, S. Dou, M. Rusckowski, and D. J. Hnatowich An experimental and theoretical evaluation of the influence of pretargeting antibody on the tumor accumulation of effector Mol. Cancer Ther., May 1, 2008; 7(5): 1025 - 1032. [Abstract] [Full Text] [PDF]

				E. F. Fidarova, E. El-Emir, G. M. Boxer, U. Qureshi, J. L.J. Dearling, M. P. Robson, R. H.J. Begent, K. R. Trott, and R. B. Pedley Microdistribution of Targeted, Fluorescently Labeled Anti-Carcinoembryonic Antigen Antibody in Metastatic Colorectal Cancer: Implications for Radioimmunotherapy Clin. Cancer Res., May 1, 2008; 14(9): 2639 - 2646. [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]

				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]

				R. M. Sharkey, H. Karacay, S. Vallabhajosula, W. J. McBride, E. A. Rossi, C.-H. Chang, S. J. Goldsmith, and D. M. Goldenberg Metastatic Human Colonic Carcinoma: Molecular Imaging with Pretargeted SPECT and PET in a Mouse Model Radiology, February 1, 2008; 246(2): 497 - 507. [Abstract] [Full Text] [PDF]

				D. M. Goldenberg, E. A. Rossi, R. M. Sharkey, W. J. McBride, and C.-H. Chang Multifunctional Antibodies by the Dock-and-Lock Method for Improved Cancer Imaging and Therapy by Pretargeting J. Nucl. Med., January 1, 2008; 49(1): 158 - 163. [Abstract] [Full Text] [PDF]

				E. El Emir, U. Qureshi, J. L.J. Dearling, G. M. Boxer, I. Clatworthy, A. A. Folarin, M. P. Robson, S. Nagl, M. A. Konerding, and R. B. Pedley Predicting Response to Radioimmunotherapy from the Tumor Microenvironment of Colorectal Carcinomas Cancer Res., December 15, 2007; 67(24): 11896 - 11905. [Abstract] [Full Text] [PDF]

				G. A.M.S. van Dongen, G. W.M. Visser, M. N. Lub-de Hooge, E. G. de Vries, and L. R. Perk Immuno-PET: A Navigator in Monoclonal Antibody Development and Applications Oncologist, December 1, 2007; 12(12): 1379 - 1389. [Abstract] [Full Text] [PDF]

				P. Macor, C. Tripodo, S. Zorzet, E. Piovan, F. Bossi, R. Marzari, A. Amadori, and F. Tedesco In vivo Targeting of Human Neutralizing Antibodies against CD55 and CD59 to Lymphoma Cells Increases the Antitumor Activity of Rituximab Cancer Res., November 1, 2007; 67(21): 10556 - 10563. [Abstract] [Full Text] [PDF]

				W. J. G. Oyen, L. Bodei, F. Giammarile, H. R. Maecke, J. Tennvall, M. Luster, and B. Brans Targeted therapy in nuclear medicine current status and future prospects Ann. Onc., November 1, 2007; 18(11): 1782 - 1792. [Abstract] [Full Text] [PDF]

				D. M. Goldenberg Proceedings of the Eleventh Conference on Cancer Therapy with Antibodies and Immunoconjugates. October 12-14, 2006. Parsippany, New Jersey, USA. Clin. Cancer Res., September 15, 2007; 13(18 Pt 2): 5499s - 5660s. [Full Text] [PDF]

				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]

				R. M. Sharkey, H. Karacay, W. J. McBride, E. A. Rossi, C.-H. Chang, and D. M. Goldenberg Bispecific Antibody Pretargeting of Radionuclides for Immuno Single-Photon Emission Computed Tomography and Immuno Positron Emission Tomography Molecular Imaging: An Update Clin. Cancer Res., September 15, 2007; 13(18): 5577s - 5585s. [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]

				G. Paganelli, M. Ferrari, L. Ravasi, M. Cremonesi, C. De Cicco, V. Galimberti, G. Sivolapenko, A. Luini, R. De Santis, L. L. Travaini, et al. Intraoperative Avidination for Radionuclide Therapy: A Prospective New Development to Accelerate Radiotherapy in Breast Cancer Clin. Cancer Res., September 15, 2007; 13(18): 5646s - 5651s. [Abstract] [Full Text] [PDF]

				J. M. Pagel, A. Pantelias, N. Hedin, S. Wilbur, L. Saganic, Y. Lin, D. Axworthy, D. K. Hamlin, D. S. Wilbur, A. K. Gopal, et al. Evaluation of CD20, CD22, and HLA-DR Targeting for Radioimmunotherapy of B-Cell Lymphomas Cancer Res., June 15, 2007; 67(12): 5921 - 5928. [Abstract] [Full Text] [PDF]

				A. R. Prideaux, H. Song, R. F. Hobbs, B. He, E. C. Frey, P. W. Ladenson, R. L. Wahl, and G. Sgouros Three-Dimensional Radiobiologic Dosimetry: Application of Radiobiologic Modeling to Patient-Specific 3-Dimensional Imaging-Based Internal Dosimetry J. Nucl. Med., June 1, 2007; 48(6): 1008 - 1016. [Abstract] [Full Text] [PDF]

				M. Jain, G. Venkatraman, and S. K. Batra Optimization of Radioimmunotherapy of Solid Tumors: Biological Impediments and Their Modulation Clin. Cancer Res., March 1, 2007; 13(5): 1374 - 1382. [Abstract] [Full Text] [PDF]

				D. M. Goldenberg Adjuvant and Combined Radioimmunotherapy: Problems and Prospects on the Road to Minerva J. Nucl. Med., November 1, 2006; 47(11): 1746 - 1748. [Full Text] [PDF]

				R. M. Sharkey Radioimmunotherapy Against the Tumor Vasculature: A New Target? J. Nucl. Med., July 1, 2006; 47(7): 1070 - 1074. [Full Text] [PDF]

				R. M. Sharkey and D. M. Goldenberg Targeted Therapy of Cancer: New Prospects for Antibodies and Immunoconjugates CA Cancer J Clin, July 1, 2006; 56(4): 226 - 243. [Abstract] [Full Text] [PDF]