Basic research on the mechanism of tumor reoxygenation after X-ray and carbon-ion irradiation

Research Project

Project/Area Number	16K10408
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Radiation science
Research Institution	National Institutes for Quantum and Radiological Science and Technology
Principal Investigator	Uzawa Akiko 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所重粒子線治療研究部, 主任研究員(定常) (90250117)
Co-Investigator(Kenkyū-buntansha)	小原麻希国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所放射線障害治療研究部, 業務補助員(任非) (80736992) 平山亮一国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所重粒子線治療研究部, 主任研究員(定常) (90435701)
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	再酸素化 / 炭素線 / X線 / 移植腫瘍 / 重粒子線 / 低酸素
Outline of Final Research Achievements	Tumor reoxygenation is an important phenomenon for overcoming radioresistant hypoxic cells. Further, if the reoxygenation can be well controlled, a shortening of treatment duration and an improvement of tumor control probability can be expected. In this study, tumor-bearing mice were irradiated with various radiations to investigate the rate of tumor reoxygenation. Reoxygenation occurred most effectively in 30 hours after Ne-ions at an LET of 80 keV/μm. On the other hand, reoxygenation after X-irradiation occurred most effectively in 54 hours.It is suggested that high LET radiation causes early tumor reoxygenation. In order to elucidate the mechanism of early reoxygenation by high LET radiation, changes in vascular density and vascular function were investigated, but these changes were not a direct factors of early reoxygenation.
Academic Significance and Societal Importance of the Research Achievements	腫瘍内の低酸素細胞は放射線に対し抵抗性を示すため、放射線がん治療において低酸素細胞への治療戦略は重要な課題である。マウス移植腫瘍に様々な放射線を照射し、腫瘍内の低酸素細胞を経時的に定量した結果、高いエネルギーを持つ重粒子線により再酸素化（低酸素状態だった細胞に酸素が届く状態になる）が早まることが示された。様々な放射線における腫瘍再酸素化現象を明らかにすることができ、再酸素化のタイミングをうまく利用することで、治療期間の短縮や腫瘍制御率の向上が期待され、腫瘍内低酸素を標的とした新しい放射線がん治療戦略の基礎知見を提供することができた。