Boron-Rich Oligophosphates — Novel Molecules for Use in BNCT

  • Robert R. Kane
  • Karin Drechsel
  • Young Soo Kim
  • Cynthia L. Beno
  • Christine S. Lee
  • Gabriel Mendez
  • Solomon Romano
  • M. Frederick Hawthorne

Abstract

For some time we1,2 and others3,4 have been interested in the use of immunoproteins for the selective localization of boron-10 in tumors. A significant challenge inherent in this approach is the requirement that each immunoprotein must be conjugated to (or otherwise associated with) approximately 103 boron-10 atoms in order to attain the necessary tumor concentrations of boron-10. Early work suggested that the development of methods for the facile synthesis of macromolecules containing large numbers of boron atoms, which we call ‘trailer’ molecules, would be necessary for the successful application of this approach to BNCT.5,6 Our research in this area has been focused upon the design of boron-rich trailers that are simple and economical to synthesize, water soluble, and homogeneous.

Keywords

Boron Atom Boron Neutron Capture Therapy Anionic Phosphate Automate Synthesis Tumor Concentration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Mizusawa, E., Dahlman, H.L., Bennett, S.J., Goldenberg, D.M. and Hawthorne, M.F., Neutron-capture therapy of human cancer: In vitro results on the preparation of boron-labeled antibodies to carcinoembryonic antigen, Proc. Natl. Acad. Sci. USA 79: 3011–3014, 1982.CrossRefGoogle Scholar
  2. 2.
    Goldenberg, D.M., Sharkey, R.M., Primus, F.J., Mizusawa, E.A., Hawthorne, M.F., Neutron-Capture Therapy of Human Cancer: In Vivo Results on Tumor Localization of Boron-10-Labeled Antibodies to Carcinoembryonic Antigen in the GW-39 Tumor Model System, Proc. Natl. Acad. Sci. 81: 560–565, 1984.PubMedCrossRefGoogle Scholar
  3. 3.
    Barth, R.F., Alam, F., Soloway, A.H., Adams, D.H., Steplewski, Z., Boronated Monoclonal Antibody 17–1A for Potential Neutron Capture Therapy of Colorectal Cancer, Hybridoma 5, Suppl. 1: S43, 1986.Google Scholar
  4. 4.
    Barth, R.F., Mafune, N., Alam, F., Adams, D.H., Soloway, A.H., Makroglou, G.E., Oredipe, O.A., Blue, T.E., Steplewski, Z., Conjucation, Purification and Characterization of Boronated Monoclonal Antibodies for Use in Neutron Capture Therapy, Strahlenther. Oncol. 165: 142, 1989.Google Scholar
  5. 5.
    Hawthorne, M.F., The Role of Chemistry in the Development of Boron Neutron Capture Therapy for Cancer, Angewandte Chemie International Edition in English 32 (7): 950–984, 1993.CrossRefGoogle Scholar
  6. 6.
    Hawthorne, M.F., Biochemical Applications of Boron Cluster Chemistry, Pure Appl. Chem. 63(3):327330, 1991.Google Scholar
  7. 7.
    Varadarajan, A., Hawthorne, M.F., Novel Carboranyl Amino Acids and Peptides: Reagents for Antibody Modification and Subsequent Neutron Capture Studies, Bioconjugate Chemistry 2: 242–253, 1991.Google Scholar
  8. 8.
    Paxton, R.J., Beatty, B.G., Varadarajan, A., Hawthorne, M.F., Carboranyl Peptide-Antibody Conjugates for Neutron-Capture Therapy: Preparation, Characterization, and in Vivo Evaluation, Bioconjugate Chemistry 3 (3): 241–247, 1992.PubMedCrossRefGoogle Scholar
  9. 9.
    Kane, R.R., Lee, C.S., Drechsel, K. and Hawthorne, M.F., Solution-Phase Synthesis of Boron-Rich Phosphates, J. Org. Chem. 58 (12): 3227–3228, 1993.CrossRefGoogle Scholar
  10. 10.
    Kane, R.R., Lee, C.S., Coe, C.L., St. Rose, M.A., Drechsel, K and Hawthorne, M.F., Novel carboranyl diols and their derived phosphate esters, in: “Advances in Neutron Capture Therapy,” A.H. Soloway, ed., Plenum Press, New York, 1993, 293–296.CrossRefGoogle Scholar
  11. 11.
    Kane, R.R., Drechsel, K., Hawthorne, M.F., Automated Syntheses of Carborane-Derived Homogeneous Oligophosphates, J. Am. Chem. Soc. 115 (19): 8853–8854, 1993.CrossRefGoogle Scholar
  12. 12.
    Gait, M. J., ed. “Oligonucleotide Synthesis: A Practical Approach,” IRL, Ltd., Oxford, 1984.Google Scholar
  13. 13.
    Drechsel, K., Lee, C.S., Leung, E.W., Kane, R.R., and Hawthorne, M.F., Synthesis of New Building Blocks for Boron-Rich Oligomers in Boron Neutron Capture Therapy (BNCT). I., Tetrahedron Lett., 35 (34): 6217–6220, 1994.CrossRefGoogle Scholar
  14. 14.
    Kane, R.R., Kim, Y.-S., unpublished results. Google Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Robert R. Kane
    • 1
  • Karin Drechsel
    • 1
    • 2
  • Young Soo Kim
    • 1
  • Cynthia L. Beno
    • 1
  • Christine S. Lee
    • 1
  • Gabriel Mendez
    • 1
  • Solomon Romano
    • 1
  • M. Frederick Hawthorne
    • 1
  1. 1.Department of Chemistry and BiochemistryThe University of California at Los AngelesLos AngelesUSA
  2. 2.Technische HochschuleAachenAachenGermany

Personalised recommendations