Novel adjuvant method of malignant brain tumor neutron capture therapy with absorbed dose evaluation and tumor localization using composite boron and high-Z element nanoparticles.

• Project/Area Number: 17K15797
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical Physics and Radiological Technology
• Research Institution: University of Tsukuba
• Principal Investigator: ZABORONOK ALEXANDER 筑波大学, 医学医療系, 助教 (20723117)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: glioma / nanoparticles / radiotherapy / radiodiagnosis / BNCT / boron / high-Z element

Outline of Final Research Achievements

Boron nanoparticles were synthesized by cascade ultrasonic dispersion / destruction of microparticles. The efficacy of the accelerator-based neutron source was proven using human and animal cells lines. Boron-related absorbed dose calculation method was tested and the unique formula was developed. As drug delivery system was crucial for targeted boron compound development, liposomal delivery was compared to standard low-molecular boron compounds in animal experiments. Our method allows in situ absorbed dose calculation using combination of boron and a High-Z element activation in the accelerator-based boron neutron capture therapy. Future implementation of our boron dose estimation method might be realized through modification of scintigraphy or isotope scanning.

Academic Significance and Societal Importance of the Research Achievements

In Japan, cancer is one of major reasons for morbidity and mortality, and the number of patients with malignant tumors is increasing year after year. The development of new forms of boron agents will move forward BNCT research and its future clinical application to extend life of cacner patients.

Research Products

• [Journal Article] Polycomplexes of Hyaluronic Acid and Borates in a Solid State and Solution: Synthesis, Characterization and Perspectives of Application in Boron Neutron Capture Therapy (2018)
  • Author(s): Zelenetskii Alexander、Uspenskii Sergey、Zaboronok Alexander、Cherkaev Georgij、Shchegolihin Alexander、Mathis Bryan、Selyanin Mikhail、Yamamoto Tetsuya、Matsumura Akira
  • Journal Title: Polymers Volume: 10 Issue: 2 Pages: 181-181
  • DOI: 10.3390/polym10020181
  • NAID: 120007134320
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Radiobiological response of U251MG, CHO-K1 and V79 cell lines to accelerator-based boron neutron capture therapy (2017)
  • Author(s): Sato Eisuke、Zaboronok Alexander、Yamamoto Tetsuya、Nakai Kei、Taskaev Sergey、Volkova Olga、Mechetina Ludmila、Taranin Alexander、Kanygin Vladimir、Isobe Tomonori、Mathis Bryan J、Matsumura Akira
  • Journal Title: Journal of Radiation Research Volume: 59 Issue: 2 Pages: 101-107
  • DOI: 10.1093/jrr/rrx071
  • NAID: 120007134126
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Boron Neutron Capture Therapy: Current State and Future Perspectives (2019)
  • Author(s): Alexander Zaboronok
  • Organizer: International Stereotactic Radiosurgery Society Webinar
  • Int'l Joint Research / Invited
• [Presentation] Hybrid gold and boron nanoparticles for treatment and boron dose estimation in boron neutron capture therapy for malignant glioma. (2018)
  • Author(s): Zaboronok A, Taskaev S, Kanygin V, Bykov T, Kasatov D, Kolesnikov I, Koshkarev A, Makarov A, Shchudlo I, Volkova O, Mechetina L, Taranin A, Kasatova A, Kichigin A, Uspenskii S, Kaptakhanova P, Zelenetskii A, Selyanin M, Bekarevich R, Mitsuishi K, Sato E, Nakai K, Tsurubuchi T, Yoshida F, Ishikawa E, Mathis BJ, et al.
  • Organizer: The 18th International Congress on Neutron Capture Therapy (ICNCT-18)
  • Int'l Joint Research
• [Presentation] Radiobiological in vitro and in vivo investigations on accelerator neutron source in Budker Institute of Nuclear Physics. (2018)
  • Author(s): Kanygin V, Kichigin A, Zaboronok A, Taskaev S, Kasatova A, Zavyalov E, Akulov A, Razumov I
  • Organizer: The 18th International Congress on Neutron Capture Therapy (ICNCT-18)
  • Int'l Joint Research
• [Presentation] Difference in BPA uptake between glioma stem cells and their cancerous cells. (2018)
  • Author(s): Yoshida F, Kurita T, Endo K, Nakai K, Shirakawa M, Zaboronok A, Ishikawa E, Matsumura A
  • Organizer: The 18th International Congress on Neutron Capture Therapy (ICNCT-18)
  • Int'l Joint Research
• [Presentation] Japan-Russia collaborative research on accelerator-based boron neutron capture therapy for malignant glioma. (2018)
  • Author(s): Zaboronok A, KanyginV, Taskaev S, Bykov T, Kasatov D, Kolesnikov J, Koshkarev A, Makarov A, Shchudlo I, Volkova O, Mechetina L, Taranin A, Kasatova A, Kichigin A, Byvaltsev V, Sato E, Nakai K, Zavjalov E, Akulov A, Ishikawa E, Mathis BJ, Yamamoto T, Matsumura A
  • Organizer: The 6th Japan Russia Neurosurgical Symposium
  • Int'l Joint Research
• [Presentation] Boron neutron capture therapy for malignant brain tumors: current situation in the world, our experience in Russia and Japan, and further development perspectives. (2018)
  • Author(s): Zaboronok A, Ishikawa E, Taskaev S, Bykov T, Kasatov D, Kolesnikov I, Koshkarev A, Makarov I, Shchudlo I, Volkova O, Mechetina L, Taranin A, Zavjalov E, Akulov A, Kanygin V, Kasatova A, Kichigin A, Byvaltsev V, Sato E, Nakai K, Mathis BJ, Yamamoto T, Matsumura A
  • Organizer: The 2nd Congress of Neurosurgeons of Uzbekistan
• [Presentation] Accelerator-based boron neutron capture therapy for malignant glioma using composite boron-gold nanoparticles: preclinical evaluation. (2018)
  • Author(s): Zaboronok A, Taskaev S, Volkova O, Mechetina L, Taranin A, Kanygin V, Zelenetskii A, Uspenskii S, Khaptakhanova P, Ishikawa E, Nakai K, Yamamoto T, Mathis BJ, Tsurubuchi T, Matsumura A.
  • Organizer: The 77th Annual Meeting of the Japan Neurosurgical Society
• [Presentation] Boron nanoparticles production by ultrasonic cavitation. (2018)
  • Author(s): Uspenskii S, Khaptakhanova P, Kurkin T, Zaboronok A, Zelenetskii A, Selyanin M, Taskaev S.
  • Organizer: The V International Conference Fundamental Bases of Mechanochemical Technologies
  • Int'l Joint Research
• [Presentation] Current state and vision of Boron neutron capture therapy (BNCT). Invited lecture. (2018)
  • Author(s): Zaboronok A
  • Organizer: Japan-Russia Joint Symposium on Education and Scientific Development in Medicine 2018
  • Int'l Joint Research / Invited
• [Presentation] Boron neutron capture therapy for malignant glioma: our experience, present status and future perspectives. (2018)
  • Author(s): Zaboronok AA, Kanygin VV, Taskaev SYu, Volkova OYu, Mechetina LV, Taranin AV, Zavjalov EL, Akulov AE, Kasatova AI, Kichigin AI, Byvaltsev VA, Sato E, Nakai K, Ishikawa E, Mathis BJ, Yamamoto T, Matsumura A
  • Organizer: The II Siberian Neurosurgical Congress
• [Presentation] Accelerator-based neutron capture therapy: pre-clinical evaluation and prospective clinical use. (2017)
  • Author(s): Zaboronok A, Kanygin V, Taskaev S, Volkova O, Mechetina L, Taranin A, Iarullina A, Kichigin A, Byvaltsev V, Sato E, Nakai K, Ishikawa E, Mathis BJ, Yamamoto T, Matsumura A.
  • Organizer: International Conference “Physics of Cancer: Interdisciplinary Problems and Clinical Applications”, Tomsk, Russian Federation, 2017.5.23-26
  • Int'l Joint Research / Invited
• [Presentation] Accelerator-based neutron capture therapy for malignant glioma with in-sample dosimetry using gold nanoparticles (2017)
  • Author(s): Zaboronok A, Taskaev S, Kanygin V, Kasatov D, Makarov A, Volkova O, Mechetina L, Taranin A, Iarullina A, Nakai K, Sato E, Mathis BJ, Yamamoto T, Matsumura A.
  • Organizer: The 32nd Japan Neurosurgery English Forum, Saitama, Japan, 2017.7.14.
• [Presentation] Perspectives of combined photodynamic diagnosis and accelerator-based neutron capture therapy of malignant glioma using photosensitizer- and 10B-containing liposomes. (2017)
  • Author(s): Zaboronok A, Taskaev S, Muhamadiyarov R, Kichigin A, Volkova O, Mechetina L, Sato E, Nakai K, Yamamoto T, Taranin A, Kanygin V, Mathis BJ, Matsumura A.
  • Organizer: 17th Annual Congress of the Korean Photodynamic Association. Seoul National University Bundang Hospital, Healthcare Innovation Park. Seoul, South Korea. 2017.09.02.
  • Int'l Joint Research
• [Presentation] Perspectives of a photosensitizer and 10B compound liposomal delivery for combined photodynamic diagnosis/therapy and accelerator-based neutron capture therapy for malignant gliomas. (2017)
  • Author(s): Zaboronok A, Taskaev S, Volkova O, Mechetina L, Kichigin A, Sato E, Nakai K, Yamamoto T, Taranin A, Kanygin V, Mathis BJ, Matsumura A.
  • Organizer: 9th Young Researchers’ BNCT Meeting. Kyoto University Uji Obaku Plaza, Gokasho, Uji, Kyoto, Japan. 2017.11.13-15.
  • Int'l Joint Research
• [Presentation] Boron neutron capture therapy for malignant glioma: our experience at the reactor and preclinical evaluation of an accelerator-based neutron source. (2017)
  • Author(s): Zaboronok AA, KanyginVV, Taskaev SYu, Volkova OYu, Mechetina LV, Taranin AV, Iarullina AI, Kichigin AI, Byvaltsev VA, Sato E, Nakai K, Zavjalov EL, Akulov AE, Ishikawa E, Mathis BJ, Yamamoto T, Matsumura A.
  • Organizer: I Congress of Eurasian Association of Pediatric Neurosurgeons. Minsk, Belarus. 2017.11.29-12.01.
  • Int'l Joint Research
• [Remarks] Webinar on BNCT by Alexander Zaboronok
  • URL: http://isrsy.org/public/en/courses/webinars/past/