62 MeV單能質子射束之相對生物效應與氧氣增強比率

Relative Biological Effectiveness and Oxygen Enhancement Ratio for a monoenergic 62-MeV therapeutic proton beam

林姿吟(Zih-Yin Lin)

指導教授 ： 蕭雅云

中山醫學大學/醫學科技學院/醫學影像暨放射科學系/碩士(2021年)

https://doi.org/10.6834/csmu202100071

摘要

輻射與細胞作用後，透過直接作用與間接作用，造成細胞DNA各種類型的損傷，可簡單分為鹼基損傷、單股螺旋斷裂與雙股螺旋斷裂。雙股螺旋斷裂屬於複雜類型的損傷，也是導致細胞死亡的主要原因。細胞針對損傷也會有不同的修復方式，修復結果也可分為正確修復、修復錯誤導致突變，也可能修復失敗而導致額外的雙股螺旋斷裂產生。這項研究的目的為利用蒙地卡羅模擬方法，模擬單能質子射束對細胞造成不同損傷與修復的情況，並研究不同氧氣條件下的雙股螺旋斷裂數量與其他生物效應的比較。
利用蒙地卡羅損傷模擬程式(Monte Carlo Damage Simulation, MCDS)及蒙地卡羅切除修復程式 (Monte Carlo Excision Repair, MCER)來進行模擬，模擬不同深度下的損傷與修復結果，得到其Total SSB (Single strand break)以及Total DSB (Double strand break)的量值(per Gy per Gbp)，也得到經由過鹼基切除修復(Base excision repair, BER)和核苷酸切除修復(Nucleotide excision repair, NER)的結果，分別為正確修復機率(correct repair)、產生突變機率(mutation)及修復失敗產生額外的雙股螺旋斷裂機率(formation of an enzymatic DSBs)。將DSB產量帶入修復固定模型(Repair-misrepair-fixation model, RMF model)中計算相對生物效應(relative biologic effectiveness, RBE)，並比較不同氧氣濃度下的RBE變化趨勢。
觀察隨組織深度增加，在MCDS損傷量的模擬結果可觀察到，鹼基損傷（Base Damage, BD）量下降3.7%，單股螺旋斷裂（Single-Strand Break, SSB）量下降1.3%，而DNA總損傷量下2.8%。簡單的損傷產量隨深度增加而呈現下降趨勢，而複雜的損傷則呈現上升趨勢。MCER模擬的修復結果，隨深度增加，正確修復的機率下降，而突變與額外產生DSB的機率呈現上升趨勢。在有氧條件下，由RMF模型計算得到的RBE值為1.0–3.0，這一數字與先前文獻實驗結果非常吻合。隨著LET增加，P1－P6的OER值從3.0降至2.5。缺氧條件下的RBE值範圍落在1.1－1.4，大於有氧條件下的RBE值，因此證明了質子的直接效應影響大於間接效應。在低氧條件下，利用誘發的DSB產量與RMF模型計算得出的RBE值分別增加7％與33％，研究結果顯示這項研究的結果表明，DSB誘發和額外產生的DSB整體作用導致更多數量的細胞死亡。

關鍵字

62MeV質子射束 ； 線性能量轉移 ； 雙股螺旋斷裂 ； 相對生物效應 ； 氧氣增強比率

並列摘要

After radiation interacts with cells, it can cause various types of DNA damage through direct and indirect effects, which can be simply divided into base damage, single strand break(SSB), and the double strand break (DSB).The DSB may play an important role in increasing the number of tumor deaths. The repair outcomes were correct repair, repair with a mutation and conversion into a DSB. This study evaluates the double strand breaks (DSBs) and misrepair in DNA to determine the relative biological effectiveness (RBE) of proton beams for DSB induction and cell survival.
All energy spectra for positions P1 to P6.The DNA damage yields are estimated using Monte Carlo Damage Simulation (MCDS) software.The Monte Carlo Excision Repair (MCER) simulates the probability of the repair outcomes in the BER and NER pathways for DNA damage in cells that are irradiated with electrons, protons and helium ions. The RBE for cell survival at different oxygen concentrations is calculated using the repair-misrepair-fixation (RMF) model. This study calculates the RBE for DSB induction and cell survival using MCDS and MCER software.
As the depth and LET increase, the yield for simpler damage, such as BD, SSB and total damage, decreases and the yield for more complex damage, such as SSB+, 2SSB, DSB, DSB+ and DSB++, increases. As the depth increases, the LET increases,and the probability of correct repair for the decreases. The probability of mutation and DSB formation respectively increase.The RBE for cell survival of protons for 6 positions increases from 1.0 to 3.0.The OER for cell survival of protons for 6 positions decreases from 3.0 to 2.5. The RBE values for extreme hypoxia (0.1% O2) are in the range of 1.1–4.4, which is greater than the RBE value for aerobic conditions, indicating greater contributions of direct effects for protons.

並列關鍵字

62 MeV proton bram ； DSB ； LET ； RBE ； OER

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