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Blood, 15 September 2007, Vol. 110, No. 6, pp. 2049-2056. Prepublished online as a Blood First Edition Paper on May 29, 2007; DOI 10.1182/blood-2007-01-066803. This Article Full Text (PDF) All Versions of this Article: blood-2007-01-066803v1 110/6/2049    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 Dahle, J. Articles by Larsen, R. H. Search for Related Content PubMed PubMed Citation Articles by Dahle, J. Articles by Larsen, R. H. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 8, 2007 Accepted May 25, 2007 Targeted cancer therapy with a novel low dose rate alpha-emitting radioimmunoconjugate Jostein Dahle*, Jorgen Borrebaek, Thora J. Jonasdottir, Anne Kristine Hjelmerud, Katrine B. Melhus, Oyvind S. Bruland, Oliver W. Press, and Roy H. Larsen Department of Radiation Biology, The Norwegian Radium Hospital, Oslo, Norway Research and Development, Algeta ASA, Oslo, Norway Small Animal Section, Department of Companion Animal Clinical Sciences, Norwegian School of Veterinary Science, Oslo, Norway University of Oslo, & Department of Oncology, The Norwegian Radium Hospital, Oslo, Norway Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, United States * Corresponding author; email: jostein.dahle{at}rr-research.no. Alpha-emitting radionuclides are highly cytotoxic and are of considerable interest in the treatment of cancer. A particularly interesting approach is in radioimmunotherapy. However, -emitting antibody conjugates have been difficult to exploit clinically due to short half-life of the radionuclides, low production capability or limited source materials. We have developed a novel technology based on the low dose rate -particle emitting nuclide 227Th, exemplified here using the monoclonal antibody rituximab. In vitro, this radioimmunoconjugate killed lymphoma cells at Bq/ml levels. A single injection of 227Th-rituximab induced complete tumor regression in up to 60 % of nude mice bearing macroscopic (32-256 mm3) human B-lymphoma xenografts at Bq/g levels without apparent toxicity. Therapy with 227Th-rituximab was significantly more effective than the control radioimmunoconjugate 227Th-trastuzumab and the standard -emitting radioimmunoconjugate for CD20 positive lymphoma, Zevalin® (90Y-tiuxetan-ibritumomab). Thorium-227 based constructs may provide a novel approach for targeted therapy against a wide variety of cancers. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Song, R. F. Hobbs, R. Vajravelu, D. L. Huso, C. Esaias, C. Apostolidis, A. Morgenstern, and G. Sgouros Radioimmunotherapy of Breast Cancer Metastases with {alpha}-Particle Emitter 225Ac: Comparing Efficacy with 213Bi and 90Y Cancer Res., December 1, 2009; 69(23): 8941 - 8948. [Abstract] [Full Text] [PDF] H. Song, K. Shahverdi, D. L. Huso, C. Esaias, J. Fox, A. Liedy, Z. Zhang, R. T. Reilly, C. Apostolidis, A. Morgenstern, et al. 213Bi ({alpha}-Emitter)-Antibody Targeting of Breast Cancer Metastases in the neu-N Transgenic Mouse Model Cancer Res., May 15, 2008; 68(10): 3873 - 3880. [Abstract] [Full Text] [PDF]

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