Impact of IUdR in rat 9L glioma cell survival for 25-35 keV photo-activated Auger electron therapy
Impact of IUdR in rat 9L glioma cell survival for 25-35 keV photo-activated Auger electron therapy
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25-35 keV 光激活俄歇电子疗法中 IUdR 对大鼠 9L 神经胶质瘤细胞存活的影响
DOI：
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Diane Alvarez
中科院分区：
文献类型：
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作者：
Diane Alvarez
....................................................................................................................................x
第1章：引言....................................................................................................1
1.1放疗技术的现状............................................................................1
1.2光激活俄歇电子疗法..........................................................................2
1.3光激活俄歇电子疗法中对高原子序数材料的要求............4
1.3.1碘苷（IUdR）在细胞内的位置..........................................................................................4
1.3.2碘苷摄取的选择性和数量......................................................................5
1.3.3产生俄歇事件的最佳单色能量和高原子序数原子..........................................................................................................................7
1.4碘苷在光激活俄歇电子疗法中的适用性....................................16
1.5碘苷的临床前和临床研究......................................................................17
1.5.1使用碘苷的常规X射线能量照射...............................................17
1.5.2使用碘苷的单色X射线能量照射...........................................18
1.6目的、假设和目标...........................................................................................23
第2章：目标1，碘苷掺入........................................................................25
2.1目标..................................................................................................................................25
2.2材料和方法........................................................................................................25
2.2.1细胞系....................................................................................................................25
2.2.2碘苷摄取研究................................................................................................26
2.2.3数据采集与分析....................................................................................29
2.3结果与讨论........................................................................................................29
第3章：目标2，细胞存活测量..................................................32
3.1目标..................................................................................................................................32
3.2测量方法和材料.............................................................................32
3.2.1 4 MV X射线照射..........................................................................................32
iv
3.2.2单色keV X射线照射..................................................................39
3.2.3细胞照射........................................................................................................55
3.3结果与讨论........................................................................................................63
3.3.1 4 MV剂量的胶片验证...............................................................................63
3.3.2单色X射线能量测量........................................................64
3.3.3离子室和胶片测量之间的剂量率比较.....................................66
3.3.4所有细胞照射数据的总结......................................................................71
第4章：目标3，细胞存活曲线的数据分析............................77
4.1目标..................................................................................................................................77
4.2方法和材料........................................................................................................77
4.2.1绘制细胞存活曲线及卡方拟合................................................77
4.2.2合并单个实验条件（E，%碘苷）下多个测量数据集的数据........................................................................78
4.2.3去除异常值....................................................................................................84
4.2.4确定10%存活率时的增敏增强比.....................85
4.3结果..............................................................................................................................89
4.3.1 4 MV数据的分析.............................................................................................89
4.3.2 35 keV数据的分析...........................................................................................89
4.3.3 30 keV数据的分析...........................................................................................94
4.3.4 25 keV数据的分析...........................................................................................94
4.3.5结果总结..................................................................................................99
4.4讨论.........................................................................................................................99
4.4.1 4 MV存活曲线..............................................................................................99
4.4.2 25 - 35 keV单色X射线的线性能量传递（LET）效应...........................................99
4.4.3碘苷作为放射增敏剂.......................................................................................103
4.4.4俄歇效应.....................................................................................................104
第5章：结论和建议....................................................108
5.1结果总结........................................................................................................108
5.2结论....................................................................................................................110
5.3对未来细胞存活测量中改进技术和方法的建议..................................................................................................110
5.4对未来细胞存活研究以阐明俄歇效应在keV照射中的作用的建议....................................................................................112
参考文献............................................................................................................................114
....................................................................................................................................x CHAPTER 1: INTRODUCTION ....................................................................................................1 1.1 Current State of the Art in Radiotherapy ............................................................................1 1.2 Photo-Activated Auger Electron Therapy ..........................................................................2 1.3 Requirements for High-Z Materials in Photo-Activated Auger Electron Therapy ............4 1.3.1 Cellular Location of IUdR ..........................................................................................4 1.3.2 Selectivity & Quantity of IUdR Uptake......................................................................5 1.3.3 Optimal Monochromatic Energy & High-Z Atom for Production of Auger Events ..........................................................................................................................7 1.4 Suitability of IUdR in Photo-Activated Auger Electron Therapy ....................................16 1.5 Pre-Clinical & Clinical Studies with IUdR ......................................................................17 1.5.1 Conventional X-Ray Energy Irradiations with IUdR ...............................................17 1.5.2 Monochromatic X-Ray Energy Irradiations with IUdR ...........................................18 1.6 Purpose, Hypothesis, & Aims...........................................................................................23 CHAPTER 2: AIM 1, IUDR INCORPORATION ........................................................................25 2.1 Goal ..................................................................................................................................25 2.2 Materials & Methods ........................................................................................................25 2.2.1 Cell Line....................................................................................................................25 2.2.2 IUdR Uptake Studies ................................................................................................26 2.2.3 Data Acquisition & Analysis ....................................................................................29 2.3 Results & Discussion ........................................................................................................29 CHAPTER 3: AIM 2, CELL SURVIVAL MEASUREMENTS ..................................................32 3.1 Goal ..................................................................................................................................32 3.2 Methods of Measurement & Materials .............................................................................32 3.2.1 4 MV X-Ray Irradiations ..........................................................................................32 iv 3.2.2 Monochromatic keV X-Ray Irradiations ..................................................................39 3.2.3 Cell Irradiations ........................................................................................................55 3.3 Results & Discussion ........................................................................................................63 3.3.1 4 MV Film Verification of Dose ...............................................................................63 3.3.2 Monochromatic X-Ray Energy Measurements ........................................................64 3.3.3 Dose Rate Intercomparison between Ion Chamber & Film Measurements .............66 3.3.4 Summary of All Cell Irradiation Data ......................................................................71 CHAPTER 4: AIM 3, DATA ANALYSIS OF CELL SURVIVAL CURVES ............................77 4.1 Goal ..................................................................................................................................77 4.2 Methods & Materials ........................................................................................................77 4.2.1 Plotting the Cell Survival Curve & Chi-Squared Fit ................................................77 4.2.2 Combining Data from Multiple Measured Data Sets for a Single Experimental Condition (E, %IUdR) ........................................................................78 4.2.3 Removing Outliers ....................................................................................................84 4.2.4 Determination of Sensitization Enhancement Ratios at 10% Survival .....................85 4.3 Results ..............................................................................................................................89 4.3.1 Analysis of 4 MV Data .............................................................................................89 4.3.2 Analysis of 35 keV Data ...........................................................................................89 4.3.3 Analysis of 30 keV Data ...........................................................................................94 4.3.4 Analysis of 25 keV Data ...........................................................................................94 4.3.5 Summary of Results ..................................................................................................99 4.4 Discussion .........................................................................................................................99 4.4.1 4 MV Survival Curves ..............................................................................................99 4.4.2 The LET Effect of 25-35 keV Monochromatic X-Rays ...........................................99 4.4.3 IUdR as a Radiosensitizer .......................................................................................103 4.4.4 The Auger Effect.....................................................................................................104 CHAPTER 5: CONCLUSIONS & RECOMMENDATIONS ....................................................108 5.1 Summary of Results........................................................................................................108 5.2 Conclusions ....................................................................................................................110 5.3 Recommendations for Improved Technology & Methodology in Future Cell Survival Measurements ..................................................................................................110 5.4 Recommendations for Future Cell Survival Studies to Elucidate the Role of the Auger Effect in keV Irradiations ....................................................................................112 REFERENCES ............................................................................................................................114
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