中性子照射中の細胞内ホウ素濃度とDNA修復効果を考慮したBNCT治療効果予測モデルの開発

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

松谷 悠佑  ; 大村 素子*; 福永 久典*

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

ホウ素中性子捕捉療法(BNCT)では、中性子とホウ素Bの核反応から発生する線やLiイオンを腫瘍に照射する。加速器型中性子線源の開発によるBNCTの普及が期待される一方、ホウ素製剤B-BPAの静脈注射投与に伴い細胞内B濃度が経時的に変化することや、加速器型BNCTの30分間以上にわたる比較的長い照射時間中に生じるDNA修復に関する影響の定量的な検討が不十分であった。そこで本研究では、細胞内B濃度変化とDNA修復効果を考慮した治療効果予測モデルを新たに開発し、これを活用して細胞生存率の詳細な解析を行った。ここで、開発したモデルにおいては、B濃度に依存する微視的線量付与(物理特性)、及び照射中のDNA損傷の修復ダイナミクス(生物過程)を考慮している。このモデルを活用した解析により、光子照射を利用する治療法よりも微視的なエネルギー付与密度が高いBNCTの場合、照射中のDNA修復効果の重要性が下がるものの、高線量照射時の腫瘍制御の低下は無視できないことも示唆された。今後、より高精度なモデル開発のために、放射線生物学的データのさらなる蓄積が望まれる。

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.