Combined Hyperthermia and Photodynamic Therapy Using a Sub-THz Gyrotron as a Radiation Source

  • Norio Miyoshi
  • Toshitaka Idehara
  • Eduard Khutoryan
  • Yukihiro Fukunaga
  • Andriana Bintang Bibin
  • Shinji Ito
  • Svilen Petrov Sabchevski
Article

Abstract

In this paper, we present results of a hyperthermia treatment of malignant tumors using a gyrotron as a radiation source for heating of the cancerous tissue. They clearly demonstrate the efficiency of the irradiation by sub-THz waves, which leads to steady decrease of the volume of the tumor and finally to its disappearance. A combination of hyperthermia and photodynamic therapy (PDT) that utilizes a novel multifunctional photosensitizer has also been explored. In the latter case, the results are even more convincing and promising. In particular, while after a hyperthermia treatment sometimes a regrowth of the tumor is being observed, in the case of combined hyperthermia and PDT such regrowth has never been noticed. Another combined therapy is based on a preheating of the tumor by gyrotron radiation to temperatures lower than the hyperthermia temperature of 43 °C and followed then by PDT. The results show that such combination significantly increases the efficiency of the treatment. We consider this phenomenon as a synergy effect since it is absent when hyperthermia and PDT are applied separately, and manifests itself only when both methods are combined.

Keywords

Sub-terahertz wave Gyrotron Hyperthermia Photodynamic therapy Cancer treatment 

Notes

Acknowledgments

One of us (N.M.) would like to thank the following persons and institutions for their support and collaboration:

i. Foundations JST and JSPS, Yuzuru Husimi (JST), Top Analysis Technology and Development of the Instrument Project (2009-2012), JSPS-Challenge & Exploratory Research (2014: 26640090), B-2 (2008-2010: 11557116), JST-Innovation (2006-2007), JSPS-Specific Research (2005-2006: 17029024), Cosmo Oil Ltd. Co. (2005-2008), JSPS-B-2 (2004-2007: 14370793), and JSPS-C-2 (1999-2000: 11672293).

ii. Clinical supports from Dr. Sadao Kaneko (Kashiwaba Neurosurgical Hospital) and Prof. Katayama.

iii. Postdoctoral researchers: Dr. Shinji Ito (Kyushu University) and Dr. Andriana Bintung Bibin (Kwansei Gakuin University, Indonesia).

iv. Collaborators from Japan and overseas: Ken-ichi Akao (Jasco Ltd. Co.), Hideki Takeda (Dai-ichi Kagaku Ltd. Co.), Dean Prof. Akira Yamaguchi, Prof. Yoshiaki Imamura, Prof. Kanji Katayama, Prof. Takanori Goi (University of Fukui), Prof. H. Hisazumi, Prof. Sukalyan Kumar Kundu (Bangladesh), Prof. Vivekananda Mandal (India), Yoichiro Ito (NIH), Dr. Kotake (USA), and Dr. P. Rietz (NIH)

Finally, this work was also supported partially by the Special Fund for Education and Research from Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan.

Compliance with Ethical Standards

All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

References

  1. 1.
    M. Thumm, “State-of-the-Art of High Power Gyro-Devices and Free Electron Masers (Update 2014),” KIT Scientific Reports, vol. 7693 (KIT Scientific Publishing), pp. 1–188, 2015.Google Scholar
  2. 2.
    Idehara T., Sabchevski S., “Development and Applications of High-Frequency Gyrotrons in FIR FU Covering the sub-THz to THz Range,” Journal of Infrared, Millimeter and Terahertz Waves, 33 (7) (2012) 667-694CrossRefGoogle Scholar
  3. 3.
    Glyavin M.Y., Idehara T., Sabchevski S.P., “Development of THz Gyrotrons at IAP RAS and FIR UF and Their Applications in Physical Research and High-Power THz Technologies,” IEEE Trans. on Terahertz Science and Technology, vol. 5, no. 5 (2015) 788–797.Google Scholar
  4. 4.
    Sabchevski S. P., Idehara T., Ishiyama S., Miyoshi N., Tatsukawa T., “A Dual-Beam Irradiation Facility for a Novel Hybrid Cancer Therapy,” Journal of Infrared, Millimeter and Terahertz Waves, 34 (1) (2013) 71-87.CrossRefGoogle Scholar
  5. 5.
    A. Doria, G.P. Gallerano, E. Giovenale, G. Messina, A. Lai, A. Ramundo-Orlando, V. Sposato, M. D’Arienzo, A. Perrotta, M. Romanò, M. Sarti, M.R. Scarfì, I. Spassovsky, O. Zen, “THz radiation studies on biological systems at the ENEA FEL facility,” Infrared Physics & Technology, 4 5 (2004) 339–347.Google Scholar
  6. 6.
    G. J. Wilmink, J. E. Grundt, Terahertz Radiation: Sources, “Applications, and Biological Effects,” In: Electromagnetic Fields in Biological Systems (Ed. James C. Lin), CRC Press (2012) 369–420.Google Scholar
  7. 7.
    [7] M. Havenith, U. Heugen, A. Bergner, S. Ebbinghaus, E. Brundermann, E. Larios, D.M. Leitner, M. Gruebele, “THz-biology: studying protein dynamics in solution,” Proc. Joint 29th Int. Conf. on Infrared and Millimeter Waves and 12th Int. Conf. on Terahertz Electronics (Karlsruhe, Germany, Sept. 27 - Oct. 1, 2004) 731–732.Google Scholar
  8. 8.
    P.H. Siegel, “Terahertz Technology in Biology and Medicine,” IEEE Trans. Microwave Theory and Techniques, 52 (2004) 2438–2447.CrossRefGoogle Scholar
  9. 9.
    A.R. Orlando, G. P. Gallerano, “Terahertz Radiation Effects and Biological Applications,” J. Infrared Millimeter and Terahertz Waves, 30 (2009) 1308–1318.Google Scholar
  10. 10.
    G. J. Wilmink, J. E. Grundt, Invited Review Article: “Current State of Research on Biological Effects of Terahertz Radiation,” J. Infrared Millimeter and Terahertz Waves, 32 (2011) 1047–1122.CrossRefGoogle Scholar
  11. 11.
    T. Tatsukawa, A. Doi, M. Teranaka, H. Takashima, F. Goda, T. Idehara, I. Ogawa, S. Mitsudo, T. Kanemaki, “Development of Submillimeter Wave Catheter Transmitting a Gyrotron Output for Irradiation on Living Bodies,” Int. J. Infrared and Millimeter Waves, 21 (2000) 1155–1167.CrossRefGoogle Scholar
  12. 12.
    T. Tatsukawa, A. Doi, M. Teranaka, H. Takashima, F. Goda, T. Idehara, I. Ogawa, T. Kanemaki, S. Nishizawa, “Submillimeter Wave Irradiation of Living Bodies using a Gyrotron and a Catheter,” Jpn. J. Appl. Phys., 41 (2002) 5486–5489.CrossRefGoogle Scholar
  13. 13.
    T. Tatsukawa, A. Doi, M. Teranaka, T. Idehara, T. Kanemaki, I. Ogawa, S.P. Sabchevski, “Submillimeter Wave Irradiation on Living Bodies Using Catheter Waveguide Vent Antennae with Dielectric Rod and Sheet”. In: NANOscale Magnetic Oxides and Bio-World, Edited by I. Nedkov and Ph. Tailhades (Heron Press Ltd., Sofia) pp. 123–138 (2004).Google Scholar
  14. 14.
    T. Tatsukawa, A. Doi, M. Teranaka, H. Takashima, F. Goda, S. Watanabe, S. Mitsudo, T. Idehara, T. Kanemaki, T. Namba, “Millimeter Wave Irradiation and Invasion into Living Bodies Using a Gyrotron as a Radiation Source,” Proc. Int. Workshop on Strong Microwaves in Plasma, 2 (2006) 727–731.Google Scholar
  15. 15.
    T. Tatsukawa, A. Doi, M. Teranaka, H. Takashima, F. Goda, S. Watanabe, T. Idehara, T. Kanemaki, T. Namba, Microwave invasion through anti-reflecting layers of dielectrics at millimeter wave irradiation to living bodies, Int. J. Infrared and Millimeter Waves, 26 (2005) 591–606.CrossRefGoogle Scholar
  16. 16.
    M. Teranaka, A. Doi, T. Tatsukawa, S. Mitsudo, T. Saito, T. Idehara, T. Kanemaki, T. Namba, “Millimeter wave irradiation and invasion into living bodies by the anti-reflecting effect,” Proc. 32nd Int. Conference Infrared, Millimeter and Terahertz Waves IRMMW-THz 2007 (2–9 Sept. 2007, Cardiff, UK) 571–572.Google Scholar
  17. 17.
    M. Teranaka, A. Doi, I. Ogawa, T. Saito, T. Idehara, T. Tatsukawa, “Millimeter wave irradiation and invasion into living bodies using AR waveguide vent antennas and Gyrotron,” Proc. 33rd Int. Conference Infrared, Millimeter and Terahertz Waves IRMMW-THz 2008 (15–19 Sept. 2008, Pasadena, CA) 1–2.Google Scholar
  18. 18.
    N. Miyoshi, Y. Fukunaga, I. Ogawa, T. Idehara, “Application for hyperthermia treatment of an experimental tumor using a gyrotron (107, 203 GHz),” Proc. 34th Int. Conference Infrared, Millimeter and Terahertz Waves IRMMW-THz 2009 (21–25 Sept. 2009, Busan, Korea) 1–2.Google Scholar
  19. 19.
    N. Miyoshi, S. Ito, I. Ogawa, T. Idehara, “Combination treatment of hyperthermia and photodynamic for experimental tumor model using gyrotron (107, 203 GHz),” Proc. 35th Int. Conference Infrared, Millimeter and Terahertz Waves IRMMW-THz 2010 (5–10 Sept. 2010, Rome, Italy) 1–2.Google Scholar
  20. 20.
    V.A. Ol’shevskaya, A.V. Zaitsev, N.D. Chkanikov, A.L. Sigan, V.N. Kalinin, Carboranyl Derivatives of Fluorinated Porphyrines and Their Metal Complexes: Photosensibilisative Properties and Preparations.//Rus. Patent No. 2402554.Google Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Norio Miyoshi
    • 1
    • 2
  • Toshitaka Idehara
    • 1
  • Eduard Khutoryan
    • 1
  • Yukihiro Fukunaga
    • 2
    • 3
  • Andriana Bintang Bibin
    • 2
    • 4
  • Shinji Ito
    • 2
    • 5
  • Svilen Petrov Sabchevski
    • 1
    • 6
  1. 1.Research Center for Development of Far-Infrared RegionUniversity of FukuiFukuiJapan
  2. 2.Division of Tumor Pathology, Department of Etiology and Pathology, Faculty of Medical SciencesUniversity of FukuiFukuiJapan
  3. 3.Research Center SBI Pharma Ltd. Co.KoubeJapan
  4. 4.Department of Biomedical Chemistry, Graduate School of Science and TechnologyKwansei Gakuen UniversitySandaJapan
  5. 5.Bio-Medical Redox Imaging Group, Innovation Center for Medical Redox NavigationKyushu UniversityFukuokaJapan
  6. 6.Institute of Electronics of the Bulgarian Academy of SciencesSofiaBulgaria

Personalised recommendations