Boron Neutron Capture Therapy Against Tumor Cells with Overexpression of the EGF-Receptor

  • Jörgen Carlsson
  • Lars Gedda
  • Christina Grönvik
  • Torbjörn Hartman
  • Annelie Lindström
  • Hans Lundqvist
  • Anna Lövqvist
  • Jonas Malmqvist
  • Pär Olsson
  • Jan Pontén
  • Stefan Sjöberg
  • Anna Sjöström
  • Bo Stenerlöw
  • Nina Tilly
  • Magnus Essand
  • Werner Tjarks
  • Bengt Westermark

Abstract

The binary nature of boron neutron capture therapy, BNCT, is an advantage because the tumor-seeking substance can be activated at any chosen time and because the neutron field can be delivered to selected areas so that exposure of critical healthy organs, which might contain significant amounts of boron, can be avoided. The tumor selective action should work in spite of the fact that tumor cells often have an infiltrative growth pattern being mixed with populations of normal cells. The targeting principle should be based on well-characterized properties of the tumor cells such as appearence of tumor-associated antigens or overexpression of receptors. The targeting agent could be antibodies, antibody-fragments or receptor ligands. Presently, mainly monoclonal antibodies are considered as targeting substances but it has been claimed that current approaches are limited by low uptake in the tumors studied. Thus, it seems necessary to also consider other principles such as growth factor mediated targeting (1–4).

Keywords

Glioma Cell Boron Neutron Capture Therapy Clonogenic Survival Boron Compound Neutron Field 
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.

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References

  1. 1.
    Carlsson, J.; Gedda L, Grönvik C, Hartman T, Lindström A, Lindström P, Lundqvist H, Lövqvist A, Malmqvist J, Olsson P, Essand M, Pontén J, Sjöberg S and Westermark B: Strategy for boron neutron capture therapy against tumor cells with over-expression of the epidermal growth factor-receptor. Int. J. Radiat. Oncol. Biol. Phys. 30 (1): 105–115, 1994.PubMedCrossRefGoogle Scholar
  2. 2.
    Andersson, A.; Capala, J.; Carlsson, J. Effects of EGF-dextran-tyrosine-31 conjugates on the clonogenic survival of cultured glioma cells. J. Neuro-Oncology 14: 213–223; 1992.CrossRefGoogle Scholar
  3. 3.
    Blomquist, E.; Carlsson, J. Strategy for planned radiotherapy of malignant gliomas. Postoperative treatments with high dose proton irradiation and tumor seeking radionuclides. Int. J. Rad. One. Biol. Phys. 22: 259–263; 1991.Google Scholar
  4. 4.
    Capala, J.; Carlsson, J. Influence of chloroquine and lidocaine on the therapeutical effects of 1311-EGF. Studies on cultured glioma cells. Int. J. Rad. Biol. 60 (3): 497–510; 1991.PubMedCrossRefGoogle Scholar
  5. 5.
    Bigner, S. H.; Burger, P. C.; Wong, A. J.; Werner, M.H.; Hamilton, S. R.; Muhlbaier, L. H.; Vogelstein, B.; Bigner, D. D. Gene amplification in malignant human gliomas: clinical and histopathologic aspects. J. Neuropathol. Exp. Neurol. 47: 191–205; 1988.PubMedCrossRefGoogle Scholar
  6. 6.
    Carpenter, G. Receptors for epidermal growth factor and other polypeptide mitogens. Ann. Rev. Biochem. 56: 881–914; 1987.CrossRefGoogle Scholar
  7. 7.
    Kern, F. G.; Cheville, A. L.; Liu, Y Growth factor receptors and the progression of breast cancer. Seminars in Cancer Biology, 1 (5): 317–328; 1990.PubMedGoogle Scholar
  8. 8.
    Liberman, T. A.; Nusbaum, H, R.; Razon, N.; Kris, R.; Lax, 1.; Soreq, H.; Whittle, N.; Waterfield, M. D.; Schlessinger, J. Amplification, enhanced expression and possible rearragement of EGF receptor gene in primary human brain tumors of glial origin. Nature 313: 144–147; 1985.Google Scholar
  9. 9.
    Murphy, L. C.; Dotzlaw, H.; Wong, M. S. J.; Miller, T.; Mroczkowski, B.; Gong, Y.; Murphy, L. J. Epidermal growth factor: receptor and ligand expression in human breast cancer. Seminars in Cancer Biology I (5): 305–316; 1990.Google Scholar
  10. 10.
    Ozawa, S.; Ueda, M.; Ando, N.; Abe, O.; Minoshima, S.; Shimzu, N. Selective killing of squamous carcinoma cells by an immunotoxin that recognizes the EGF receptor. Int. J. Cancer 43 (1): 152–157; 1989.Google Scholar
  11. 11.
    Prigent, S. A.; Lemoine, N. R. The type 1 (EGFR-related) family of growth factor receptors and their ligands. Progress in Growth Factor Res. 4: 1–24; 1992.CrossRefGoogle Scholar
  12. 12.
    Malmqvist, J.; Sjöberg, S. Synthesis of some w-aminoalkyl-1,2-closo-dicarbado-decaboranes (12). Inorganic Chem. 31: 2534–2537; 1992.CrossRefGoogle Scholar
  13. 13.
    Pettersson, O.; Olsson, P.; Lindström, R; Sjöberg, S.; Carlsson, J. Penetration and binding of L- and D-carboranylalanine in human melanoma spheroids. Melanoma Res. 3 (5): 1–8; 1993.CrossRefGoogle Scholar
  14. 14.
    Varadarajan, A.; Hawthorne, M. F. Novel carboranyl amino acids and peptides: reagents for antibody modification and subsequent neutron capture studies. Bioconjugate Chem. 2: 242–253; 1991.CrossRefGoogle Scholar
  15. 15.
    Sjöberg, S.; Hawthorne, M. F.; Lindström, P.; Malmquist, J.; Carlsson, J.; Andersson, A.; Pettersson, O. Assymetric synthesis of carboranyl amino acids with potential use in BNCT. In “Neutron Capture Therapy”. Editors: Soloway, A. H., Barth R. F. and Carpenter D. E., pp 269–272. Plenum Press, New York, 1993.CrossRefGoogle Scholar
  16. 16.
    Wcisboeck, R. A.; Hawthorne, M. F. Dicarbaundecaborane (13) and derivatives. J. Am. Chem. Soc. 86: 1642–1643; 1964.CrossRefGoogle Scholar
  17. 17.
    Andersson, A.; Holmberg A.; Carlsson, J.; Carlsson, J.; Pontén, J.; Westermark, B. Binding of epidermal growth factor-dextran conjugates to cultured glioma cells. Int. J. Cancer 47: 439–444; 1991.PubMedCrossRefGoogle Scholar
  18. 18.
    Lövqvist, A., Lindström, A.; Carlsson, J. Binding, internalization and excretion of TGFa-dextran associated radioactivity in cultured human glioma cells. Cancer Biotherapy, 8 (4): 345–356, 1993.PubMedCrossRefGoogle Scholar
  19. 19.
    Olsson, P.; Lindström, A.; Carlsson, J. Internalization and excretion of epidermal growth factor-dextran associated radioactivity in cultured human squamous carcinoma cells. Int. J. Cancer, 56: 529–537; 1994.Google Scholar
  20. 20.
    Haigler, H. T.; Maxfield, F. R.; Willingham, M. C.; Pastan, I. Dansylcadaverine inhibits internalization of ‘251-epidermal growth factor in BALB 3T3 cells. J. Biol. Chem. 855: 1239–1241; 1980.Google Scholar
  21. 21.
    Capala, J.; Prahl, M.; Scott-Robson, S.; Pontén, J.; Westermark, B.; Carlsson, J. Effects of 1311-EGF on cultured human glioma cells. J. Neuro-Oncology 9: 201–210; 1990.CrossRefGoogle Scholar
  22. 22.
    Scott-Robson, S.; Capala, J.; Carlsson, J.; Malmborg, P.; Lundqvist, H. Distribution and stability in the rat of a 76Br/1251 labelled polypeptide, epidermal growth factor. Int. J. applied Radiation and Isotopes, Nucl. Med. Biol. 18 (2): 241–246; 1991.Google Scholar
  23. 23.
    Lindström, A.; Lundqvist, H.; Carlsson, J. Distribution of 125I after administration of 1251-labelled epidermal growth factor-dextran conjugates in mice. Acta Universitatis Upsaliensis, Vol.: 428: chapter 5; 1993.Google Scholar
  24. 24.
    Escher, E.; Leukart, O.; Kriwaczek, V. M. L-carboranylalanine substituted TM V. A highly boron labelled virus as a model for slow neutron therapy of tumors. J. of Labelled Compounds and Radiopharmaceuticals 14: 487–496; 1978.CrossRefGoogle Scholar
  25. 25.
    Carlsson, J.; Sjoberg, S.; Larsson, B. Present Status of Boron Neutron Capture Therapy. Acta Oncologica 31: 803–814; 1992.PubMedCrossRefGoogle Scholar
  26. 26.
    Larsson, B. Neutron capture therapy in support of other radiation treatment. In: Clinical aspects of neutron capture therapy, eds.: Fairchild, R., G., Bond V. R. and Woodhead A.V., pp. 21–26. New York: Plenum Publishing Corp. 1989.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Jörgen Carlsson
    • 1
  • Lars Gedda
    • 1
  • Christina Grönvik
    • 1
  • Torbjörn Hartman
    • 1
  • Annelie Lindström
    • 1
  • Hans Lundqvist
    • 1
  • Anna Lövqvist
    • 1
  • Jonas Malmqvist
    • 2
  • Pär Olsson
    • 1
  • Jan Pontén
    • 3
  • Stefan Sjöberg
    • 2
  • Anna Sjöström
    • 1
  • Bo Stenerlöw
    • 1
  • Nina Tilly
    • 1
  • Magnus Essand
    • 1
  • Werner Tjarks
    • 2
  • Bengt Westermark
    • 3
  1. 1.Department of Radiation SciencesUppsala UniversityUppsalaSweden
  2. 2.Department of ChemistryUppsala UniversityUppsalaSweden
  3. 3.Department of PathologyUppsala UniversityUppsalaSweden

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