利用快速蒙地卡羅演算法計算鄂惹電子發射體誘發的DNA損傷

近31年來，惡性腫瘤一直在台灣國人十大死因中高居榜首，如何更有效的治療癌症成為了眾人關心的課題。放射性的腫瘤標靶治療能夠有效的針對特定的腫瘤細胞進行治療，利用例如免疫標誌的方式，將放射性核種送到目標的腫瘤細胞附近，使腫瘤能夠更準確、更加集中的接受到放射劑量，而達到殺死腫瘤細胞，治癒癌症的目的；因此選用一個合適的核種去進行治療成為一個值得研究的方向。過去的研究對於能夠發射出鄂惹電子的核種，對於細胞所造成的生物效應感到十分感興趣，為了能夠更好的去評估各種核種在放射治療上的潛力，我們提出了一個利用局部損傷模型的演算法，使用這個模型為將能夠發射出鄂惹電子的核種均勻分佈在細胞中，以同心球體的方式將細胞分成多層結構，用以計算核種在各層所造成的局部劑量，進而得到核種在細胞中造成的吸收劑量，以及核種單次衰變對於細胞造成各種形式的DNA損傷產率。選用了五種核種去進行評估，分別為：125I、119Sb、123I、111In和 99mTc，使用了兩種蒙地卡羅方法：先利用Penolope code對於各個核種放出的鄂惹電子對於細胞產生的細胞S值進行計算，這個混合型的演算法結合了事件對事件方法(event by event)、以及多重散射理論模型(multiple scattering theory)，能對於非常低能量的電子進行模擬；使用MCDS(Monte Carlo Damage simulation )code計算不同能量對於細胞造成各種形式的DNA損傷的產率，MCDS測量的方式是利用從詳細的軌道結構模擬(track structure)的方式得到的趨勢性，從而計算DNA的損傷。將使用這種計算法所得到的細胞S值以及DNA損傷的產率與過去已經發表的資料去做比較，細胞S值所得到的結果與利用其他數學分析法、蒙地卡羅方法、實驗結果的資料比較後的差異範圍大概會是在8%以內，而結合兩個演算法得到的結果與其他已經發表的資料比較起來，大致上的結果是準確的，雖然會有點誤差性存在，這個方法可以藉由MCDS得到的結果，評估各個核種之間的相對生物效應，對於核種的選擇上提供幫助。這種方式我們認為是能夠有效，並且可以使用各種能夠發射鄂惹電子核種的頻譜，預測在不同的環境結構下，例如：單層細胞模型，得到各核種所造成各種不同DNA損傷的產率。希望在未來對於放射性腫瘤標靶治療方式的核種選擇上，能夠提供一個有效且方便的計算法。

關鍵字

鄂惹電子；蒙地卡羅方法； DNA損傷；相對生物效應

並列摘要

In this thesis, an algorithm methodology was proposed to estimate the absorbed does to help selecting a suitable nuclide on radionuclide target therapy. Past studies were interested in the biological effectiveness on cells by the Auger-electron emitting nuclides. As to radiation treatment, for a better estimation on therapeutic potential of various types of radionuclide, we proposed an algorithm by used local damage model. Used this model, the radiation source was assumed to be uniform distributed over cells in the way of concentric spheres to divide cells into multiple-shell structure. We could calculate the absorbed does produced by nuclide on each structural shell of cells, and various types of DNA clustered damage yields by per decay of radionuclide. We chose the five kinds of radionuclides to estimate: 125I, 119Sb, 123I, 111In, and 99mTc, and use two kinds Monte Carlo code. First of all, by way of Penolope (Penetration and ENErgy LOss of Positrons and Electrons) code , we could calculate the subcellular absorbed dose and cellular S value from radiation by each Auger-electrons emitting radionuclide. This mixed simulation algorithm combined an event by event simulation for hard collisions and multiple scattering theory for soft collisions, could be simulated for very low energy electrons. Monte Carlo damage simulation (MCDS) damage simulation code was applied to estimate the nucleotide-level maps of clustered DNA damage yields caused by different energy. To estimate the DNA damage data, MCDS employed the tendency of the DNA damage spectrum from the detailed track structural simulation ,such method will relatively simple and efficient. The calculated S value and DNA damage yields had been compared with published data. The estimated cellular S values outcome would be probably less than 8% discrepancy of previous outcome from other mathematical analysis, Monte Carlo method and the experimental data. Compared with other published data, the outcome from the combination of two algorithms, was generally found accurate although some discrepancy existed. In terms of the MCDS outcome, this method could evaluate the relative biological effectiveness of each radionuclide and assist in the selection of radionuclide.

並列關鍵字

Auger electrons ； monte carlo method ； DNA damage ； relative biological effectiveness

參考文獻

Ager DD, Dewey WC, Gardiner K, Harvey W, Johnson RT,Waldren CA 1990 Measurement of radiation-induced DNA double-strand Breaks by pulsed-field gel electrophoresis Radiat Res.122 181-187

Baró J, Sempau J, Fernández-Varea JM and Salvat F 1995 PENELOPE: an algorithm for Monte Carlo simulation of the penetration and energy loss of electrons and positrons in matter Nucl. Instrum Methods Phys. Res. B 100 31-46

Belli M, Cherubini R, Dalla Vecchia M, Dini V, Moschini G, Signoretti C, Simone G, Tabocchini MA, Tiveron P. 2000 DNA DSB induction and rejoining in V79 cells irradiated with light ions: a constant field gel electrophoresis study Int J Radiat Biol. 76 1095-1104

Bernhardt P, Forssell-Aronsson E, Jacobsson L, Skarnemark,G 2001 Low-energy Electron Emitters for Targeted Radiotherapy of Small Tumours. J. Nucl. Med. 40 602-608

Bousis C, Emfietzoglou D, Hadjidoukas P, Nikjoo H 2010 Monte Carlo single-cell dosimetry of Auger-electron-emitting radionuclides. Phys. Med. Biol. 55 2555-2572

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利用快速蒙地卡羅演算法計算鄂惹電子發射體誘發的DNA損傷

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