Implications of radiation microdosimetry for accelerator-based boron neutron capture therapy; A Radiobiological perspective

Fukunaga, Hisanori*; Matsuya, Yusuke; Tokuue, Koichi*; Omura, Motoko*

British Journal of Radiology, 93(1111), p.20200311_1 - 20200311_4, 2020/07

https://doi.org/10.1259/bjr.20200311

Boron neutron capture therapy (BNCT) has attracted attention as a selective treatment approach for cancer cells while sparing surrounding normal cells. The basic concept of BNCT was developed in the 1930s, but it has not yet been commonly popular in clinical practice, even though there is now a large number of experimental and translational studies demonstrating its marked therapeutic potential. With the development of neutron accelerators that can be installed in medical institutions, accelerator-based BNCT is expected to become available at several medical institutes around the world in the near future. In this commentary, from the point of view of microdosimetry, we discuss the biological effects of BNCT, especially the underlying mechanisms of cell responses. The recent development of new treatment methods that combine proton beam sources and BNCT technology is expected to contribute significantly improving the prognosis of cancer treatment in the near future. Therefore, radiobiologists in the field of BNCT and related techniques will have a significant role to play in creating synergy effects in clinical oncology.

The Small-molecule Bcl-2 inhibitor HA14-1 sensitizes cervical cancer cells, but not normal fibroblasts, to heavy-ion radiation

Hamada, Nobuyuki*; Kataoka, Keiko*; Sora, Sakura*; Hara, Takamitsu*; Omura, Motoko*; Funayama, Tomoo; Sakashita, Tetsuya; Nakano, Takashi*; Kobayashi, Yasuhiko

Radiotherapy and Oncology, 89(2), p.227 - 230, 2008/11

https://doi.org/10.1016/j.radonc.2008.08.006

Heavy-ion microbeam irradiation induces bystander killing of human cells

Hamada, Nobuyuki*; Hara, Takamitsu*; Omura, Motoko*; Ni, M.*; Funayama, Tomoo; Sakashita, Tetsuya; Sora, Sakura*; Nakano, Takashi*; Kobayashi, Yasuhiko

Uchu Seibutsu Kagaku, 22(2), p.46 - 53, 2008/10

https://doi.org/10.2187/bss.22.46

HA14-1, an inhibitor of Bcl-2, may sensitize tumor cells to heavy ions

Hamada, Nobuyuki*; Kataoka, Keiko*; Sora, Sakura*; Hara, Takamitsu*; Funayama, Tomoo; Sakashita, Tetsuya; Omura, Motoko*; Kobayashi, Yasuhiko

no journal, , 

no abstracts in English

Killing of Bcl-2 overexpressing tumor cells by -rays and heavy charged particles

Hara, Takamitsu*; Hamada, Nobuyuki*; Omura, Motoko*; Sakashita, Tetsuya; Wada, Seiichi*; Kobayashi, Yasuhiko

no journal, , 

no abstracts in English

Heavy-ion irradiation overcomes the radioresistance of tumor cells overexpressing Bcl-2

Hamada, Nobuyuki*; Hara, Takamitsu*; Funayama, Tomoo; Sakashita, Tetsuya; Kataoka, Keiko*; Sora, Sakura; Suzuki, Michiyo; Fukamoto, Kana; Yokota, Yuichiro; Omura, Motoko*; et al.

no journal, , 

no abstracts in English

Development of a model to predict BNCT therapeutic effects in consideration of intracellular boron concentration and DNA repair during neutron irradiation

Matsuya, Yusuke; Omura, Motoko*; Fukunaga, Hisanori*

no journal, , 

Boron neutron capture therapy (BNCT) is a treatment method enabling selectively eradicating tumors by -particles and Li ions generated through the nuclear reaction between neutrons and B within tumor cells. While the accelerator-based neutron source has been developed, the intracellular B concentration dynamically changes after intravenous injection of the boron into patients, and the neutron-delivery time is relatively long for 30 minutes or more. However, the quantitative analysis for investigating the impacts of DNA repair during irradiation on curative effects is insufficient. In this study, we developed a mathematical model for predicting the therapeutic effects that considers the change in intracellular B concentration and DNA repair, and performed detailed analysis. The model developed in this study considers the following two factors: one is microdosimetric quantities (physical characteristics) that depends on B concentration, and the other is DNA repair dynamics (biological process) during irradiation. The model estimation results exhibits that the importance of DNA repair during irradiation is reduced in the case of BNCT with a higher dose at sub-cellular scale than photons. It was also suggested that the DNA repair effects on tumor control cannot be ignored even in the case of BNCT. In the future, further accumulation of radiobiological data is desired for improving models.

Bcl-2 as a potential target for heavy-ion therapy

Hamada, Nobuyuki*; Hara, Takamitsu*; Kataoka, Keiko*; Sora, Sakura*; Omura, Motoko*; Funayama, Tomoo; Sakashita, Tetsuya; Yokota, Yuichiro; Kobayashi, Yasuhiko

no journal, , 

no abstracts in English