2017 Fiscal Year Research-status Report
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
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| Research Institution | University of Tsukuba |
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Principal Investigator |
ザボロノク アレクサンドル 筑波大学, 医学医療系, 助教 (20723117)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Keywords | BNCT / glioma / nanoparticles / boron / high-Z element |
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| Outline of Annual Research Achievements |
In 2017 fiscal year, the following stages of the main plan were accomplished. Composite boron and high-Z element (gold)-containing nanoparticles were synthesized by a new proposed method of cascade ultrasonic dispersion / destruction of micron particles (analyzed by X-ray crystallography) in an aqueous medium. Optical characteristics were analyzed by the light absorption and dynamic light scattering (DLS), showing particle size distribution, zeta-potential and the plasmon resonance. The particles were studied using transmission (TEM) and surface electronic microscopy (SEM). Elemental analysis was performed using inductively-coupled plasma atomic emission spectroscopy (ICP-AES). The efficacy of the accelerator-based neutron source was proven using human and animal tumor and normal cell lines by exponential decrease in colony formation with increase in boron concentration.The method of absorbed dose estimation using combination of boron and gold in tumor cells was tested using human glioma cells with incubated high-Z element nanoparticles and irradiated by epithermal neutrons in an acryl phantom to mimic real treatment conditions.Sample activation resulted in radioactive 198Au isotope generation which was utilized for absorbed dose calculations at each boron concentration.The overall cell-killing effect of the therapy was assessed by a colony-forming assay with evaluation of radiobiological parameters. The results of the study were presented at several conferences and included in scientific publications.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
Implementation of the main plan was slightly delayed due to the limited machine time at the exclusive accelerator-based neutron source and initial procedures of development of absolutely unique nanoparticles, production method and evaluation of the product types prior to application in boron neutron therapy (BNCT) experiments.At the initial stage of the development of a nano-sized composite boron-high-Z-element-compound for BNCT, the funds were also partly spent on transportation to the accelerator-based neutron source as neutron irradiation was required for main stages of the study. Further publishing and manuscript-related costs are planned to be covered in the next fiscal year.
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| Strategy for Future Research Activity |
The funds will be used according to the main plan of the study, including all preparatory stages of the study flow, with additional costs for publications, transferred to the next fiscal year.Further evaluation of the composite compounds presented as boron and high-Z element-containing nanoparticles in vivo for their toxicity, accumulation in tumor and normal tissues, the tumor/normal tissue accumulation ratio, tumor killing effect (decrease in size or disappearance of the tumor) and the effect on healthy tissues will be performed. Additionally, boron dose estimation in the irradiated tumor tissue and development of tumor localization using the properties of the high-Z element in the composite compounds will be done. Animal (rat and/or mouse) subcutaneous and/or brain tumor models of animal and human brain tumors are planned to be used. Selection of the most appropriate and less toxic compound with better accumulation in tumor tissues and higher tumor to normal tissue ratio, as well as better boron dose estimation properties is planned. Selection of more treatment-sensitive tumors for chosen compounds with further modification of the composite compounds to improve their functionality is planned to advance the research towards future clinical application.
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[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
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[Presentation] Accelerator-based neutron capture therapy for malignant glioma with in-sample dosimetry using gold nanoparticles2017
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.
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[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
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[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
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[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
