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Selective Thermal Neutron Capture Therapy of Cancer Cells Using their Specific Metabolic Activities—Melanoma as Prototype

  • Yutaka Mishima

Abstract

It was around 1972 when it occurred to me that the accentuated melanogenesis occurring parallel and specific to the transformation of pigment cells to malignant melanoma could be utilized if we successfully synthesized and administered a10B-melanogenesis-seeking compound such as 10B-DOPA analogue (described later) into melanoma patients followed by thermal neutron irradiation. The 10B (n,α)7 Li reaction then would be specifically induced within10B-rich melanoma cells, leading to a novel selective melanoma eradication therapy. The success of such thermal neutron capture therapy (NCT) could be a good prototype leading to selective therapy for all cancers having specific metabolic activities. After completion of many years of basic investigative studies1~12 we successfully treated the first human malignant melanoma proliferating in the occipital region of a 66 year old man in 1987. This life threatening metastatic lesion soon showed complete regression following a single application, thus enabling us to attempt NCT on even operable cases. Thereafter, the total number of patients successfully treated by us using this therapy amounts to 18.

Keywords

Melanoma Cell Pigment Cell Boron Neutron Capture Therapy Relative Biological Effectiveness Positron Emission Tomography 
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.
    Y. Mishima, M. Ichihashi, K. Hayashibe, M. Ueda, S. Hatta, Y. Funasaka, and G. Imokawa, Control of melanogenesis and melanoma oncogenesis, in: “Advances in Pigment Cell Research,” J.T. Bagnara, ed., Alan R. Liss, Inc., New York, 1988, pp. 127–141.Google Scholar
  2. 2.
    Y. Mishima, A post melanosomal era: control of melanogenesis and melanoma growth. Pigment Cell Research Suppl. 2: 3–16, 1992.Google Scholar
  3. 3.
    Y. Mishima, Molecular and biological control of melanogenesis—through tyrosinase genes. and intrinsic & extrinsic regulatory factors — Presidential Address at XVth International Pigment Cell Conference, London, Sept. 26–30, 1993, Pigment Cell Research, 7: 376–387, 1994.PubMedCrossRefGoogle Scholar
  4. 4.
    Y. Mishima, “Melanoma Neutron Capture Therapy”, Alan R. Liss, New York, 1989, pp. 1–385.Google Scholar
  5. 5.
    K. Yoshino, A. Suzuki, Y. Mori, H. Kakihana, C. Honda, Y. Mishima, T. Kobayashi, and K. Kanda, Improvement of solubility of p-boronophenylalanine by complex formation with monosaccharides, Strahlenther Onkol., 165: 127–129, 1989.PubMedGoogle Scholar
  6. 6.
    K. Yoshino, M. Okamoto, H. Kakihana, Y. Mori, Chemical assay of boron and its distribution in melanoma-bearing subjects, in: “Neutron Capture Therapy”, H. Hatanaka, ed., Nishimura, Niigata, 1986, pp. 291–302.Google Scholar
  7. 7.
    K. Taniyama, H. Fujiwara, T. Kuno, N. Saito, H. Shuntoh, M. Sakaue, and C. Tanaka, Acute and subacute toxicity of 10B-paraboronophenylalanine, Pigment Cell Research, 2: 291–296, 1989.PubMedCrossRefGoogle Scholar
  8. 8.
    Y. Mishima, M. Ichihashi, C. Honda, M. Shiono, T. Nakagawa, H. Obara, J. Shirakawa, J. Hiratsuka, K. Kanda, T. Kobayashi, T. Nozaki, O. Aizawa, T. Sato, H. Karashima, K. Yoshino, and H. Fukuda, Advances in the control of human cutaneous primary and metastatic melanoma by thermal neutron capture therapy, in: “Progress in Neutron Capture Therapy for Cancer,” B.J. Allen, D.E. Moore, and B.V. Harrington eds. Plenum Press, New York, 1992, pp. 577–583.CrossRefGoogle Scholar
  9. 9.
    C. Honda, M. Shiono, N. Wadabayashi, M. Ichihashi, Y. Mishima, T. Kobayashi, K. Kanda, Y. Fiori, and K. Yoshino, Increased selective 10B-uptake by malignant melanoma using systematic administration of 10B,-BPA.fructose complex, in: “Progress in Neutron Capture Therapy for Cancer,” B.J. Allen. D.E. Moore, and B.V. Harrington eds, Plenum Press, New York, 1992, pp. 421–424.CrossRefGoogle Scholar
  10. 10.
    M. Shiono, T. Shibata, M. Ichihashi, and Y. Mishima, The mechanism of the selective affinity of 1°B,paraboronophenylalanine for malignant melanoma, Kyoto University Research Reactor Institute Technical Report. 374: 59–65, 1993.Google Scholar
  11. 11.
    M. Shiono, T. Shibata, C. Honda, N. Wadabayashi, M. Ichihashi, Y. Hori, K. Yoshino, and Y. Mishima, In vivo cellular pharmacology on the selective affinity of 10B1-BPAfor malignant melanoma, in: “Progress in Neutron Capture Therapy for Cancer,” B.J. Allen, D.E. Moore, and B.V. Harrington eds, Plenum Press, New York, 1992, pp. 439–442.CrossRefGoogle Scholar
  12. 12.
    K Yoshino, Y Mori, H Kakihana, H Takahashi, M. Ichihashi, and Y. Mishima, Chemical modeling for boron accumulation to and release from melanoma, in: “Cancer Neutron Capture Therapy,” Y. Mishima ed, Plenum Press, New York, 1996.Google Scholar
  13. 13.
    H. Madoc-Jones, R. Zamenhof, G. Solares, O. Harling, C-S. Yam, K. Riley, S. Kiger, D. Wazwe, G. Rogers, and M. Atkins, A phase-I dose-escalation trial of boron neutron capture therapy for subjects with metastatic subcutaneous melanoma of the extremities, in: “Cancer Neutron Capture Therapy,” Y. Mishima ed, Plenum Press, New York, 1996.Google Scholar
  14. 14.
    J.A. Coderre, G.M. Morris, P.L. Micca, M.M. Nawrocky, C.D. Fisher, A. Bywaters and J.W. Hopewell, The therapeutic ratio in BNCT: Assessment using the rat 9L gliosarcoma brain tumor and spinal cord models, in: “Cancer Neutron Capture Therapy,” Y. Mishima ed, Plenum Press, New York, 1996.Google Scholar
  15. 15.
    J.A. Coderre, J.D. Glass, R.G. Fairchild, U. Roy, S. Cohen, and I. Fand, Selective targeting of boronophenylalanine to melanoma in BALB/c mice for neutron capture therapy, Cancer Research, 47: 6377–6383, 1987.PubMedGoogle Scholar
  16. 16.
    Y. Mishima, Y. Imahori, C. Honda, J. Hiratsuka, S. Ueda, and T. Ido, In vivo diagnosis of human malignant melanoma with positron emission tomography using specific melanoma-seeking 15F-dopa analogue, J. Neuro-Oncology, 1996,in press.Google Scholar
  17. 17.
    R.F. Barth, K.Z. Matalka, M.Q. Bailey, A.E. Staubus, A.H. Soloway, M.L. Moeschberger, J.A. Coderre, and E.K. Rofstad, A nude rat model for neutron capture therapy of human intracebral melanoma, Int. J. Radiation Oncology Biol. Phys., 28: 1079–1088, 1994.CrossRefGoogle Scholar
  18. 18.
    J.A. Coderre, D.D. Joel, P.L. Micca, M.M. Nawrocky, and D.N. Slatkin, Control ofintracebral gliosarcomas in rats by boron neutron capture therapy with p-boronophenylalanine, Radiation Research, 129: 290–296, 1992.PubMedCrossRefGoogle Scholar
  19. 19.
    H. Hatanaka, and Y. Nakagawa, Clinical results of long-surviving brain tumor patients who underwent boron neutron capture therapy, Int. J. Radiation Oncology Biol. Phys., 28: 1061–1066, 1994.CrossRefGoogle Scholar
  20. 20.
    M. Ichihashi, A. Sasase, T. Hiramoto, Y. Funasaka, S. liana, Y. Mishima, T. Kobayashi, H. Fukuda, and K. Yoshino, Relative biological effectiveness (RBE) of thermal neutron capture therapy of cultured f3–16 cells preincubated with 10B-paraboronophenylalanine, Pigment Cell Research, 2: 325–329. 1989.PubMedCrossRefGoogle Scholar
  21. 21.
    J. Hiratsuka, M. Kono. and Y. Mishima, RBEs of [hernial neutron capture therapy and 1“B(n,u)’Li reaction of melanoma-bearing hamsters, Pigment Cell Research, 2: 352–355, 1989.PubMedCrossRefGoogle Scholar
  22. 22.
    Y. Mishima, M. Ichihashi, M. Tsuji, S. Hatta, M. Ueda, C. Honda, and T. Suzuki, Treatment of malignant melanoma by selective thermal neutron capture therapy using melanoma-seeking compound, J. Invest. Dermatol., 92: 3215–3255, 1989.CrossRefGoogle Scholar
  23. 23.
    Y. Mishima, M. Ichihashi, S. Hatta, C. Honda, K. Yamamura, and T. Nakagawa, New thermal neutron capture therapy for malignant melanoma: Melanogenesis-seeking 10B molecule-melanoma cell interaction from in vitro to first clinical trial, Pigment Cell Research, 2: 226–234, 1989.PubMedCrossRefGoogle Scholar
  24. 24.
    T. Kobayashi and K. Kanda, Microanalysis system of ppm-order 15B concentrations in tissue capture therapy by prompt gamma-ray spectrometry, Nuclear Instruments Methods, 204: 525–531, 1983.CrossRefGoogle Scholar
  25. 25.
    Y. Mishima, C. Honda, M. Ichihashi, H. Obara. J. Hiratsuka, Il. Fukuda, I I. Karashima, T. Kobayashi, K. Kanda, and K. Yoshino, Treatment of malignant melanoma by single neutron capture treatment with melanoma-seeking 10B-Compound. Lancet 11: 388–389, 1989.CrossRefGoogle Scholar
  26. 26.
    H. Fukuda, J. Hiratsuka, C. Honda, T. Kobayashi, K. Yoshino, H. Karashima, J. Takahashi, Y. Abe, K. Kanda, M. Ichihashi, and Y. Mishima, Boron neutron capture therapy of malignant melanoma using 10B-paraboronophenylalanine with special reference to evaluation of radiation close and damage to the normal skin. Radiai Res 138: 435–442, 1994.CrossRefGoogle Scholar
  27. 27.
    K. Ishiwata, T. Ido, M. Kawamura, K. Kubota, M. Ichihashi, and Y. Mishima, 4-Borono-2-[15F] fluoroD-L-phenylalanine as a target compound for boron neutron capture therapy: tumor imaging potential with positron emission tomography. Nucl Med Biol, 18: 745–751, 1991.Google Scholar
  28. 28.
    K. Ishiwata, M. Shiono, K. Kubota, K. Yoshino, J. Hatazawa, T. Ido. C. Honda, M. Ichihashi, and Y. Mishima, A unique in vivo assessment of 4-[10B]borono-L-phenylalanine in tumor tissues for boron neutron capture therapy of malignant melanomas using positron emission tomography and 4-horono-2[18F]fluoro-L-phenylalanine. Melanoma Res, 2: 171–179, 1992.PubMedCrossRefGoogle Scholar
  29. 29.
    K. Ishiwata, T. Ido, C. Honda, M. Kawamura, M. Ichihashi, and Y. Mishima. 4-Borono-2-[1“F] fluoroD,L-phenylalanine: a possible tracer for melanoma diagnosis with PET. Nue/.3-led Biol, 19: 311–318, 1992.Google Scholar
  30. 30.
    K. Kanda and Y. Mishima, Nuclear reactors for medical use, J. -aronde Energy Soc. Japan, 35: 371–372, 1993.Google Scholar
  31. 31.
    Y. Mishima, Summary of investigation results, in: “Investigation of the Nuclear Reactor for Cancer Therapy ”(1)-(5); Report of Cooperative Research Under Grant-in-Aid of The Ministry of Education, Science and Culture, Japan, 1989–1983.Google Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Yutaka Mishima
    • 1
  1. 1.Mishima Institute for Dermatological ResearchKobe 657Japan

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