质子治疗对细胞自由基产额影响的蒙特卡罗模拟计算

Monte Carlo Simulation of the Effect of Proton Therapy on Free Radical Yield in Cell

随着质子FLASH治疗等新兴放疗技术的发展,细胞受辐照后生物学效应的不确定性成为急需解决的难题。由于缺乏对物理-化学阶段机理的完整理解,目前的模拟工作仍然以调整化学参数使自由基产额与实验数据相匹配为主。作为一个不断发展的蒙特卡罗软件,Geant4能够在纳米尺度上模拟入射粒子在短时间内通过物理和化学相互作用引起水分子辐解的过程。基于Geant4软件构建了一个简易的细胞模型,模拟了细胞靶体内自由基产额受辐射粒子影响的情况,并对靶内自由基产额的变化趋势进行了详细计算。研究表明,随着LET的逐渐增大,自由基OH^(·)的数目占比从25%下降到10%左右。当考虑质子FLASH透射治疗时,使用25%的自由基OH^(·)数目占比作为化学损伤参数去评估细胞DNA损伤将会更为合理。同时,两种活性氧自由基O_(2)^(·)和O_(2)^(-)在超高剂量率下的产额G(t)随模拟时间的发展都出现了不同程度的升高。研究结果阐明了不同治疗深度下细胞靶体内自由基产额随时间和粒子能量的变化情况,揭示了模拟工作中质子FLASH治疗在布拉格峰区和坪区应该采用不同的化学损伤参数。

With the development of new particle radiotherapy techniques such as proton FLASH therapy,the uncertainty of the biological effects after cell irradiation has become an urgent problem to be solved.Due to the lack of a complete understanding of the physico-chemical stage mechanism,the current simulation work is still mainly based on adjusting the chemical parameters to match the simulated free radical yield with the experimental data.As an evolving Monte Carlo software,Geant4 is able to simulate on the nanoscale the radiolysis process of water molecules caused by incident particles through physical and chemical interactions in a short period of time.In this work,a simplified tumor cell model was designed based on Geant4 software to simulate the free radical yield in the cell target affected by radiation particles,and the ratio of free radical yield in the target was calculated in detail.The results show that with the gradual increase of linear energy transfer(LET),the proportion of free radical OH^(·)numbers production will decrease from 25%to about 10%.When proton transmission FLASH is considered,it is more reasonable to use the 25%radical OH^(·)ratio as a chemical damage parameter to evaluate cell DNA damage.Based on the oxygen effect theory,the yield G of two reactive oxygen species,O_(2)^(·)and O_(2)^(-),both increased to varying degrees with the development of simulation time at ultra-high dose rates.The results elucidate the variation of free radical yield in cell targets under different treatment depths and reveal that proton FLASH therapy in the Bragg peak and flat region should be used for different chemical damage parameters.