中华放射医学与防护杂志

孙健涵,孔祥慧,吕建锋,等.FLASH放疗中不同氧含量下束流时间结构驱动的自由基动力学研究[J].中华放射医学与防护杂志,2025,45(11):1061-1068.Sun Jianhan,Kong Xianghui,Lyu Jianfeng,et al.Study on the radical kinetics driven by the beam time profile under different oxygen contents in FLASH radiotherapy[J].Chin J Radiol Med Prot,2025,45(11):1061-1068

FLASH放疗中不同氧含量下束流时间结构驱动的自由基动力学研究

Study on the radical kinetics driven by the beam time profile under different oxygen contents in FLASH radiotherapy

投稿时间：2025-06-24

DOI：10.3760/cma.j.cn112271-20250624-00213

中文关键词: FLASH放射治疗自由基蒙特卡罗模拟束流物理

英文关键词:FLASH radiotherapy Free radicals Monte Carlo simulation Beam physics

基金项目:国家自然科学基金(12275012,12475309,12411530076,12375334,12581360004,82202941);北京市自然科学基金(Z210008);国家重点研发计划项目(2019YFF01014402);北京大学肿瘤医院临床研究青年基金(QNJJ2023018);中央高校基本科研业务费/北京大学临床医学+X青年专项(PKU2025PKULCXQ014);教育部内地与港澳高等学校师生交流计划项目(万人计划7111400072);内蒙古自治区科技计划项目(2022YFSH0064)

作者	单位	E-mail
孙健涵	北京大学核物理与核技术国家重点实验室北京大学物理学院, 北京 100871 北京大学肿瘤医院暨北京市肿瘤防治研究所放疗科恶性肿瘤发病机制及转化研究教育部重点实验室, 北京 100142
孔祥慧	香港理工大学医疗科技及资讯学系, 香港 999077
吕建锋	北京大学核物理与核技术国家重点实验室北京大学物理学院, 北京 100871 北京激光加速创新中心, 北京 101407
王景辉	北京激光加速创新中心, 北京 101407 广东省新兴激光等离子体技术研究院, 广州 510540
刘小冬	中国石油大学(华东)化学化工学院应用化学系, 青岛 266580
林晨	北京大学核物理与核技术国家重点实验室北京大学物理学院, 北京 100871 北京激光加速创新中心, 北京 101407
黎田	香港理工大学医疗科技及资讯学系, 香港 999077
张艺宝	北京大学肿瘤医院暨北京市肿瘤防治研究所放疗科恶性肿瘤发病机制及转化研究教育部重点实验室, 北京 100142
黄森林	北京大学核物理与核技术国家重点实验室北京大学物理学院, 北京 100871	huangsl@pku.edu.cn

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中文摘要:

目的揭示束流时间结构与组织氧含量对自由基动力学的耦合作用机制, 进而解释FLASH效应的潜在生物学基础, 并为FLASH放疗的束流优化和计划设计提供参考。方法使用TOPAS-nBio v3.0模拟电子束在水中产生的物理与化学作用过程, 建立涵盖羟基自由基 ( ·OH) 和水合电子(e_aq^-)等自由基生成、扩散、反应与猝灭的全尺度动力学模型。在不同束流时间结构(单脉冲、多脉冲、连续波照射)及不同氧浓度条件下, 系统模拟自由基演化动态。同时, 通过实验测试激光吸收光谱获取e_aq^-含量数据, 验证模型预测的准确性。结果实验测得的e_aq^-浓度变化趋势与模拟结果高度一致, 验证了所构建模型的可靠性。束流时间结构对自由基浓度峰值与持续时间具有显著影响, 单脉冲结构可导致自由基短时间内快速升高后迅速猝灭, 而连续或长脉冲结构则引起自由基浓度在较长时间内维持较高水平。·OH的演变对氧环境不敏感, 而e_aq^-则受氧环境影响剧烈。低氧环境下e_aq^-自由基清除效率明显下降, 导致生物大分子的氧化损伤累积增强。富氧环境下e_aq^-寿命快速缩短。结论自由基动力学受到束流时间结构和氧含量的双重调控。FLASH放疗可以利用单脉冲或多脉冲间隙期形成周期性窗口, 正常组织通过高效抗氧化清除自由基降低损伤, 而肿瘤组织中自由基持续累积并放大损伤, 从而产生选择性保护效应。

英文摘要:

Objective To reveal the coupling mechanism of beam temporal profile and tissue oxygen content on radical kinetics, further explain the potential biological basis of the FLASH effect, and provide a reference for beam optimization and treatment planning design of FLASH radiotherapy (FLASH-RT). Methods TOPAS-nBio v3.0 was used to simulate the physical and chemical processes of electron beams in water, and a full-scale kinetic model was established covering the generation, diffusion, reaction, and quenching of free radicals such as hydroxyl radical (·OH) and hydrated electrons (e_aq^-). Under different beam temporal profiles (single pulse, multi-pulses, continuous wave irradiation) and different oxygen concentration conditions, the evolution dynamics of free radicals were systematically simulated. At the same time, the data on e_aq^- content were obtained by experimental measurement of laser absorption spectroscopy to verify the accuracy of the model prediction. Results The changing trend of e_aq^- concentration measured in the experiment was highly consistent with the simulation result, verifying the reliability of the constructed model. The beam time structure had a significant impact on the peak value and duration of free radical concentration. The single-pulse structure can cause the free radicals to rapidly increase and then quickly quench in a short time, while the continuous or long-pulse structure can cause the radical concentration to remain at a high level for a long time. The evolution of ·OH was not sensitive to the oxygen environment, while e_aq^- are greatly affected by the oxygen environment. The scavenging efficiency of free radicals in a hypoxic environment was significantly decreased, leading to an enhanced accumulation of oxidative damage to biological macromolecules. The lifespan of e_aq^- in an oxygen-rich environment decreased rapidly. Conclusions Radical kinetics are regulated by both the beam temporal profile and oxygen content. FLASH-RT can utilize single-pulse or multi-pulses intervals to form periodic windows, reducing normal tissue damage by efficiently scavenging free radicals through antioxidants, while free radicals in tumor tissues continuously accumulate and amplify damage, thus generating a selective protective effect.

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