TY - JOUR

T1 - Boron-neutron capture therapy in russia

T2 - Preclinical evaluation of efficacy and perspectives of its application in neuro-oncology

AU - Zaboronok, Alexander Anatolyevich

AU - Byvaltsev, V. A.

AU - Kanygin, V. V.

AU - Iarullina, A. I.

AU - Kichigin, A. I.

AU - Taranin, A. V.

AU - Yu, Volkova O.

AU - Mechetina, L. V.

AU - Yu, Taskaev S.

AU - Muhamadiyarov, R. A.

AU - Zavyalov, E. L.

AU - Nakai, K.

AU - Sato, E.

AU - Yamamoto, T.

AU - Mathis, B. J.

AU - Matsumura, A.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Boron-neutron capture therapy is a unique form of adjuvant cancer therapy for various malignancies including primary malignant brain tumors, and especially glioblastoma, characterized by the fastest and most aggressive type of growth. The main advantage of boron-neutron capture therapy is the selective destruction of tumor cells without harming normal tissues. Clinical trials have shown that boron-neutron capture therapy is a promising treatment method of various malignancies. The use of nuclear reactors in therapy is unfeasible from a safety standpoint. Therefore, relatively safe accelerator-based epithermal neutron sources for boron-neutron capture therapy are in worldwide development. The accelerator-based epithermal neutron source constructed in Budker Institute of Nuclear Physics in Novosibirsk (Russia) offers a unique opportunity to test this new therapy method. Joint teams of physicists, biologists and medical doctors carry outmultiple experiments to assess the efficacy of the accelerator-based epithermal neutron source to be further used in preclinical and clinical trials, the results of which are presented in this article. To determine optimal irradiation conditions and evaluate the effect of boron-neutron capture therapy on tumor cell survival, experiments were conducted on human glioma cell line (U251MG). The cells were incubated in medium with boronophenylalanine and irradiated by epithermal neutron flux. Boron-negative cells, irradiated by neutrons, as well as those cells, which weren’t irradiated by neutrons were used as controls. The colony forming assay showed that generated neutron flux doesn’t affect cell viability without boron and is effective in treating tumor cells, in which boron is accumulated. Experimental studies on the influence of neutron flux and boron neutron capture therapy on animals depending on the radiation dose were conducted. The study included severe combined immunodeficiency mice pretreated with sodium borocaptate. Control group included animals without boron administration and without irradiation. Dynamic monitoring on the condition of the animals was performed. Evaluation of tissue damage was carried out using histological examinations. The result of the experiment revealed that the neutron flux in therapeutic doses doesn’t affect the condition of the animals, and the dose to healthy tissues of immunodeficient mice during irradiation is tolerant. The study present a novel method of boron drug delivery to the tumor tissue by means of pegylated liposomes with a fluorescent label, which can increase the efficacy of boron-neutron capture therapy and determine the localization of the compound in tissues.

AB - Boron-neutron capture therapy is a unique form of adjuvant cancer therapy for various malignancies including primary malignant brain tumors, and especially glioblastoma, characterized by the fastest and most aggressive type of growth. The main advantage of boron-neutron capture therapy is the selective destruction of tumor cells without harming normal tissues. Clinical trials have shown that boron-neutron capture therapy is a promising treatment method of various malignancies. The use of nuclear reactors in therapy is unfeasible from a safety standpoint. Therefore, relatively safe accelerator-based epithermal neutron sources for boron-neutron capture therapy are in worldwide development. The accelerator-based epithermal neutron source constructed in Budker Institute of Nuclear Physics in Novosibirsk (Russia) offers a unique opportunity to test this new therapy method. Joint teams of physicists, biologists and medical doctors carry outmultiple experiments to assess the efficacy of the accelerator-based epithermal neutron source to be further used in preclinical and clinical trials, the results of which are presented in this article. To determine optimal irradiation conditions and evaluate the effect of boron-neutron capture therapy on tumor cell survival, experiments were conducted on human glioma cell line (U251MG). The cells were incubated in medium with boronophenylalanine and irradiated by epithermal neutron flux. Boron-negative cells, irradiated by neutrons, as well as those cells, which weren’t irradiated by neutrons were used as controls. The colony forming assay showed that generated neutron flux doesn’t affect cell viability without boron and is effective in treating tumor cells, in which boron is accumulated. Experimental studies on the influence of neutron flux and boron neutron capture therapy on animals depending on the radiation dose were conducted. The study included severe combined immunodeficiency mice pretreated with sodium borocaptate. Control group included animals without boron administration and without irradiation. Dynamic monitoring on the condition of the animals was performed. Evaluation of tissue damage was carried out using histological examinations. The result of the experiment revealed that the neutron flux in therapeutic doses doesn’t affect the condition of the animals, and the dose to healthy tissues of immunodeficient mice during irradiation is tolerant. The study present a novel method of boron drug delivery to the tumor tissue by means of pegylated liposomes with a fluorescent label, which can increase the efficacy of boron-neutron capture therapy and determine the localization of the compound in tissues.

KW - Accelerator-based epithermal neutron source

KW - Boron delivery agents

KW - Boron-neutron capture therapy

KW - Colony forming assay

KW - Glioma

UR - http://www.scopus.com/inward/record.url?scp=85018346180&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:85018346180

VL - 11

SP - 6

EP - 15

JO - New Armenian Medical Journal

JF - New Armenian Medical Journal

SN - 1820-0254

IS - 1

ER -