Radiobiological effects of novel brachytherapy using alfa-radiation sources for oral cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03886
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: MIURA MASAHIKO 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (10272600)
• Co-Investigator(Kenkyū-buntansha): 宇尾 基弘 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (20242042) ; 戒田 篤志 東京医科歯科大学, 東京医科歯科大学病院, 助教 (40632097) ; 小野里 祐佑 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (10844300)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 口腔がん / 小線源治療 / α線源

Outline of Final Research Achievements

Diffusing alpha-emitters radiation therapy (Alpha-DaRT) is a unique method, in which interstitial sources carrying Ra-224 release a chain of short-lived daughter atoms from their surface. Although DNA damage response (DDR) is crucial to inducing cell death after irradiation, how the DDR occurs during Alpha-DaRT treatment has not yet been explored. In this study, we temporo-spatially characterized DDR such as kinetics of DNA double-strand breaks (DSBs) and cell cycle, in two-dimensional (2D) culture conditions qualitatively mimicking Alpha-DaRT treatments, by employing HeLa cells expressing the Fucci cell cycle-visualizing system. A medium containing daughter nuclides prepared from Ra-224 sources allowed us to estimate the radiation dose after 24 h of exposure, and determine surviving fractions. The present experimental model revealed for the first time temporo-spatial information of DDR occurring around the source in its early stages and we attempted to apply the data to clinics.

Free Research Field

放射線生物学、放射線腫瘍学、歯科放射線学

Academic Significance and Societal Importance of the Research Achievements

Diffusing alpha-emitters radiation therapy (Alpha-DaRT)は、現在PMDAによる承認間近な状況となっている。しかしながら、基礎的な検討は十分になされていなかった。そこで、本研究では、細胞周期、DNA損傷、α粒子を可視化する方法を導入して早期のDNA損傷応答を可視化したところ、FucciによるG2アレスト細胞が、他の指標よりより高感度に検出されることがわかり、今後の前臨床試験を実施する上で、治療による有効性を確認するための有用な指標となりうることが示唆された。