臺灣博碩士論文加值系統

硼 中 子 捕 獲 治 療(boron neutron capture therapy，簡稱BNCT)是癌病治療中最具潛力的一種方法。其原理係將含有硼-10 ( 10B )的藥物導入腫瘤組織中，再以超熱中子(epithermal neutron)由體外對病患腫瘤部位進行照射。當超熱中子進入人體後經由能量的衰減，到達腫瘤組織時已減速為熱中子。由於熱中子與硼-10之間的捕獲截面(capture cross-section)非常大，約為3800邦，而產生的阿伐粒子及鋰-7 重荷電粒子的射程大約與細胞的大小相當，又因為這兩種粒子的游離密度高，所以，當含硼藥物很理想地集中分佈在腫瘤細胞中時，腫瘤組織便能有效的被殺死而不會影響相鄰的正常組織。
BNCT 的最大優點乃在於硼中子捕獲作用產生之高游離密度的重荷電粒子，在相同吸收劑量的條件下，比起低游離密度之輻射粒子的相對生物效應(relative biological effectiveness，簡稱RBE)大，造成DNA雙鍵斷裂(double strand break)的機會高，當然殺死癌細胞的效果也就愈好。要評估 BNCT在腫瘤組織及正常組織的生物劑量，必須用微劑量學(microdosimetry)的方法，來研究中子與腫瘤組織及正常組織作用產生之所有二次輻射粒子(包括阿伐粒子，鋰-7 重荷粒子，反彈質子，貝它粒子，光子等)，在細胞靶(target)內的微觀(microscopic)能量分布，以暸解細胞靶中吸收能量的微觀統計變化，作為評估RBE及生物劑量的依據。
本論文的研究重點在於評估：含硼藥物在細胞中分佈對細胞核的劑量貢獻的影響，做為BNCT的動物實驗前試驗。

Boron neutron capture therapy (BNCT) is a targeted radiation therapy that significantly increases the therapeutic ratio relative to conventional radiotherapeutic modalities. A boron -10(10B)-labeled compound is administered that transports densely concentrations of 10B to the target tumor relative to surrounding normal tissues. Subsequently followed by irradiation with thermal neutrons or epithermal neutrons, the short ranges of the alpha and 7Li particles released from the 10B(n , alpha)7Li reaction are so short that if tumor cells accumulate the boron compound selectively, only tumor cells can be killed. As the effectiveness of BNCT in killing tumor cells relies on the number of 10B atoms delivered to tumor, and the subcellular distribution of 10B and the thermal neutron fluence at the site of the tumor, the pharmaceutical distribution in tumor cells greatly affects the performance of BNCT. Monte Carlo calculations of the energy depositions of short-range particles with high LET coming from 10B disintegration were performed. This simulation permits us to study the influence of the allocation of intracellular 10B in cytoplasm, or nucleoplasm, or on cell membranes, or on contiguous cells.
We demonstrate here a Monte Carlo computer model incorporating the following elements:
1. To simplify geometry of tumor cells, we assume all of the following tumor cells having a spherical geometry shape in this simulation. Then, using Monte Carlo computation corrects the pharmaceutical distribution in the spherical geometry shape cell model.
2.Selective the dimensions in nucleus and in cell.
3.Input the absorbed fractions of boron only in cytoplasm, or nucleoplasm , or on cell membranes, or on contiguous cells.
We can obtain various GAF (geometric adjustment factor) causing from different portions (the localization of boron in cytoplasm, or nucleoplasm , or on cell membranes, or on contiguous cells ) . As to that, we would estimate how the pharmaceutical distribution affects the performance of BNCT.

第一章 前言……………………………………………………………..1
第二章 程式模擬原理及方法…………………………………………..7
2.1蒙地卡羅模擬原理………………………………………………...7
2.2 簡單細胞模型的模擬…………………………….………….….10 2.2.1 硼中子捕獲作用發生在細胞膜上時……………………………11
2.2.2硼中子捕獲作用發生在細胞質中時……………………….14
2.2.3 硼中子捕獲作用發生在細胞核內時………………………16
2.2.4 硼中子捕獲作用發生在相鄰細胞上時……………………18
2.2.5 阿伐粒子、鋰-7重荷電粒子的射程與能量關係表….……21
第三章 實驗原理及方法………………………………………………24
3.1物理實驗…………………….…………….……….….….……..24
3.1.1中子活化分析(Neutron Activation Analysis)….………….. 24
3.1.1.1 原理……………………………………………… ……24
3.1.1.2 實驗步驟……………………………………………….26
3.1.2 熱發光劑量計校正及THOR射束中加馬劑量……………27
3.1.2.1 原理……………………………………………… ……27
3.1.2.2 實驗步驟………………………………………… ……28
3.2生物實驗………………………………………………………….30
3.2.1 細胞種類及配置……………………………………………30
3.2.1.1化學藥品配置…………………………………… …….30
3.2.1.2 細胞種類……………………………………………….30
3.2.1.3 細胞培養條件………………………………………….31
3.2.2 游離輻射對細胞的傷害實驗……………………………..32
3.2.2.1 簡介…………………………………………………….32
　 3.2.2.2 實驗步驟 ……………………………………………...33
3.2.3細胞毒性測試MTT比色分析法( MTT assay)……………37
3.2.4細胞的硼中子捕獲作用…………………………………….38
第四章 結果與討論………………………………………………… ...39
4.1 程式模擬結果………………………………………………… ..39
4.1.1含硼藥物在細胞膜上時，對細胞核造成的能量沉積….. ..39
4.1.2含硼藥物在細胞質內時，對細胞核造成的能量沉積……..39
4.1.3含硼藥物在細胞核內時，對細胞核造成的能量沉積……..39
4.1.4含硼藥物在相鄰細胞間時，對細胞核造成的能量沉積……39
4.1.5 GAF模擬值………………………………………………….40
4.2 中子活化分析結果…………………………………………….. 41
4.3 熱發光劑量計校正結果及THOR射束中加馬劑量實測值… .43
4.3.1 TLD-700靈敏度校正……………………………………….43
4.3.2 TLD-700劑量校正曲線…………………………………….44
4.3.3 THOR 射束中加馬的劑量度量……………………………45
4.3.4 THOR中子及加馬劑量率的模擬………………………….47
4.3.5 THOR中子及加馬劑量率的實測值……………………… 47
4.4 THOR射束對細胞的生存率影響………………………………48
4.4.1 THOR對NFsa 細胞的生存率影響……………………… 48
4.4.2 THOR對Tramp 細胞的生存率影響…………………….. 52
4.5 60Co 對細胞的生存率影響……………………………………...55
4.5.1 60Co 對NFsa細胞的生存率影響………………………… ..55
4.5.2 60Co 對Tramp細胞的生存率影響…………………………56
4.6 細胞對10B的毒性測試………………………………………….58
4.6.1 Tramp細胞對10B的毒性測試………………………………59
4.6.2 NFsa細胞對10B的毒性測試……………………………. …61
4.7 硼中子捕獲對細胞存活率的影響……………………………...63
第五章 結論……………………………………………………………66
參考文獻………………………………………………………………..67

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