Biological elucidation and construction of clinical application for next-generation proton beam FLASH irradiation utilizing differences in LET

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07682
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Nagoya City University
• Principal Investigator: Hiromitsu Iwata 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (40611588)
• Co-Investigator(Kenkyū-buntansha): 歳藤 利行 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (30377965)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: FLASH / 超高線量率照射 / LET / 陽子線

Outline of Final Research Achievements

We adjusted ultra-high dose rate irradiation (FLASH) by varying the LET with a synchrotron accelerator, established technical precision, and confirmed SOBP formation. A chick embryo chorioallantoic membrane assay was introduced to verify the efficacy and toxicity mitigation effects of FLASH. In the SOBP region, a decrease in mitigation effects was observed. The accuracy of FLASH irradiation was validated using Monte Carlo simulations. In Drosophila, phenotypic differences such as inflammation were confirmed using a microassay. In vitro, an increase in apoptosis and cell cycle delay were observed. Due to the effects of LET, FLASH irradiation at the peak showed a reduction in toxicity mitigation effects and an increase in cytotoxic effects. We achieved an expansion of the irradiation field for real clinical application using scanning irradiation

Free Research Field

陽子線治療

Academic Significance and Societal Importance of the Research Achievements

日本国内で初めてシンクロトロン加速器を使用した陽子線の超高線量率照射(FLASH)を実現した。実臨床応用のため、技術的精度の確立やin vitro、in vivoにおいてFLASH効果や癌組織における各種表現型の評価を行い、メカニズム解析を進めた。FLASH照射のエネルギーを変えることで、LET 付与の高い SOBP(spread-out Bragg peak)を形成することができ、正常組織や癌に対する影響の違いを初めて確認した。今後さらに、研究が進むことで、陽子線治療や難治性の癌治療の発展・普及に大いに寄与すると考えられる。