SEARCH:   Advanced

Blood, 1 July 2004, Vol. 104, No. 1, pp. 227-236. Prepublished online as a Blood First Edition Paper on March 2, 2004; DOI 10.1182/blood-2003-09-3284. This Article Full Text (PDF) All Versions of this Article: 2003-09-3284v1 104/1/227    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 Forero, A. Articles by Meredith, R. F Search for Related Content PubMed PubMed Citation Articles by Forero, A. Articles by Meredith, R. F Social Bookmarking                   What's this? Submitted October 3, 2003 Accepted January 30, 2004 Phase I trial of a novel anti-CD20 fusion protein in pretargeted radioimmunotherapy for B-cell non-Hodgkin's lymphoma Andres Forero*, Paul L Weiden, Julie M Vose, Susan J Knox, Albert F LoBuglio, Jordan Hankins, Michael L Goris, Vincent J Picozzi, Don B Axworthy, Hazel B Breitz, Robert B Sims, Richard G Ghalie, Sui Shen, and Ruby F Meredith Medicine, Division of Hematology/Oncology, University of Alabama at Birmingham, Comprehensive Cancer Center, Birmingham, AL, USA Virginia Mason Medical Center, Seattle, WA, USA University of Nebraska Medical Center, Omaha, NE, USA Stanford University Medical Center, Palo Alto, CA, USA NeoRx Corporation, Seattle, WA, USA * Corresponding author; email: Andres.forero{at}ccc.uab.edu. Pretargeted® radioimmunotherapy (PRIT) has the potential to increase the dose of radionuclide delivered to tumors while limiting radiation to normal tissues. The purpose of this phase I trial is to assess safety of this multi-step approach using a novel tetrameric single-chain anti-CD20/Streptavidin fusion protein (B9E9FP) as the targeting moiety in patients with B cell NHL, and to characterize its pharmacokinetics and immunogenicity. All patients received B9E9FP (160 or 320 mg/m2); either 48 or 72 hours later, a synthetic clearing agent (sCA) was administered (45 mg/m2) to remove circulating unbound B9E9FP; 90Y(15 mCi/m2)/111In(5 mCi) DOTA-Biotin was injected 24 hours later. Fifteen patients were enrolled. The B9E9FP had a mean plasma T1/2 of 25±6 hours with a reduction in plasma level >95% within 6 hours of sCA administration. 90Y/111In-DOTA-Biotin infusion resulted in rapid tumor localization and urinary excretion. The ratio of average tumor to whole body radiation dose was 49. No significant hematological toxicities were noted in 12 patients. Two patients had hematologic toxicity related to progressive disease. Two complete remissions (90 and 325 days) and 1 partial response (297 days) were seen. B9E9FP performs well as the targeting component of PRIT with encouraging dosimetry, safety and efficacy. A dose escalation trial of 90Y-DOTA-Biotin in this format is warranted. 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. 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] A. Iagaru, S. S. Gambhir, and M. L. Goris 90Y-Ibritumomab Therapy in Refractory Non-Hodgkin's Lymphoma: Observations from 111In-Ibritumomab Pretreatment Imaging J. Nucl. Med., November 1, 2008; 49(11): 1809 - 1812. [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] F. Buchegger, O. W. Press, A. B. Delaloye, and N. Ketterer Radiolabeled and Native Antibodies and the Prospect of Cure of Follicular Lymphoma Oncologist, June 1, 2008; 13(6): 657 - 667. [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] R. F. Meredith, S. Shen, A. Forero, and A. LoBuglio A Method to Correct for Radioactivity in Large Vessels That Overlap the Spine in Imaging-Based Marrow Dosimetry of Lumbar Vertebrae J. Nucl. Med., February 1, 2008; 49(2): 279 - 284. [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. 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] A. Pantelias, J. M. Pagel, N. Hedin, L. Saganic, S. Wilbur, D. K. Hamlin, D. S. Wilbur, Y. Lin, D. Stone, D. Axworthy, et al. Comparative biodistributions of pretargeted radioimmunoconjugates targeting CD20, CD22, and DR molecules on human B-cell lymphomas Blood, June 1, 2007; 109(11): 4980 - 4987. [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] T. C. Chu, K. Y. Twu, A. D. Ellington, and M. Levy Aptamer mediated siRNA delivery Nucleic Acids Res., June 1, 2006; 34(10): e73 - e73. [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] 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] R. M. Reilly Radioimmunotherapy of Solid Tumors: The Promise of Pretargeting Strategies Using Bispecific Antibodies and Radiolabeled Haptens J. Nucl. Med., February 1, 2006; 47(2): 196 - 199. [Full Text] [PDF] G. J. Kelloff, K. A. Krohn, S. M. Larson, R. Weissleder, D. A. Mankoff, J. M. Hoffman, J. M. Link, K. Z. Guyton, W. C. Eckelman, H. I. Scher, et al. The Progress and Promise of Molecular Imaging Probes in Oncologic Drug Development Clin. Cancer Res., November 15, 2005; 11(22): 7967 - 7985. [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] R. M. Sharkey, H. Karacay, T. M. Cardillo, C.-H. Chang, W. J. McBride, E. A. Rossi, I. D. Horak, and D. M. Goldenberg Improving the Delivery of Radionuclides for Imaging and Therapy of Cancer Using Pretargeting Methods Clin. Cancer Res., October 1, 2005; 11(19): 7109s - 7121s. [Abstract] [Full Text] [PDF] A. V. Rao, G. Akabani, and D. A. Rizzieri Radioimmunotherapy for Non-Hodgkin's Lymphoma Clin. Med. Res., August 1, 2005; 3(3): 157 - 165. [Abstract] [Full Text] [PDF] S. Shen, A. Forero, A. F. LoBuglio, H. Breitz, M.B. Khazaeli, D. R. Fisher, W. Wang, and R. F. Meredith Patient-Specific Dosimetry of Pretargeted Radioimmunotherapy Using CC49 Fusion Protein in Patients with Gastrointestinal Malignancies J. Nucl. Med., April 1, 2005; 46(4): 642 - 651. [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] S. Modak and N.-K. V. Cheung Antibody-Based Targeted Radiation to Pediatric Tumors J. Nucl. Med., January 1, 2005; 46(1_suppl): 157S - 163S. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020