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Monte Carlo Simulations and Experiments of Metal Nanoparticle Enhanced Low-Energy Radiotherapy : 금속나노입자 저에너지 방사선치료를 위한 몬테카를로 시뮬레이션과 실험

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dc.contributor.advisor예성준-
dc.contributor.advisor김일한-
dc.contributor.author성원모-
dc.date.accessioned2018-05-28T16:53:58Z-
dc.date.available2018-05-28T16:53:58Z-
dc.date.issued2018-02-
dc.identifier.other000000149806-
dc.identifier.urihttps://hdl.handle.net/10371/140973-
dc.description학위논문 (박사)-- 서울대학교 대학원 : 융합과학기술대학원 융합과학부, 2018. 2. 예성준|김일한.-
dc.description.abstractThe goal of radiation therapy is to deliver therapeutic doses to tumors while sparing surrounding normal tissue. Even though various techniques such as intensity-modulated radiation therapy (IMRT) have been introduced, increasing the therapeutic ratio is still a challenging goal in radiation cancer treatment. Over the last decade, the radiosensitizing potential of nanoparticles (NPs) has shown great promise. Interests in this field have particularly focus on gold nanoparticles (GNPs) due to its biocompatibility and high atomic number. However, macroscopic radiation dose calculations by mass energy absorption fail to predict observed experimental findings on level of radiosensitization and GNP concentrations.
The purpose of this dissertation is to investigate whether dose inhomogeneities induced by GNPs on a cellular scale is a source of GNPs mediated radiosensitization. First, the feasibility of nanoparticle-enhanced Auger therapy was evaluated regarding electron energy spectra, microscopic dose distributions, and biological effectiveness using the S-value. Second, for nanoparticle-enhanced external photon therapy, biological effectiveness was systemically assessed in the various cell and nucleus geometry with GNPs. Radiation dose dependence of cell survival with GNPs was observed experimentally and predicted theoretically. The realistic modeling with 3D distributions of GNPs in live cells was established as observed by optical diffraction tomography (ODT).
We performed Monte Carlo simulations to characterize interactions between GNPs and low-energy photons at the nanometer scale. Calculated radiation dose was applied to a biological model to quantify the GNP radiosensitization. Due to a steep radial dose falloff within short distances from the GNPs (<1% of the surface dose at 100 nm), geometric parameters such as the shape, size, and location of the cell, nucleus, and GNPs are important to assess GNP enhanced radiation therapy. GNP – Local Effect Model was established based on live cell images and showed good agreement with observed radiation response in the presence of GNPs.
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dc.description.tableofcontentsChapter I. Introduction 1
1. Basic Principles of Radiation Therapy 2
2. Basic Principles of Radiosensitization 6
3. Nanoparticles-Mediated Radiosensitization 9

Chapter II. Nanoparticle Enhanced Auger Therapy 15
Abstract 15
1. Introduction 16
2. Material and Methods 18
2.A. Monte Carlo Simulation 18
2.B. Simulation of Nanoparticles Structures 21
2.B.a. Case1: Nanoshell 21
2.B.b. Case2: Nanosphere 22
2.B.c. Elements of Nanoparticles 22
2.C. Cellular S-values 23
3. Results 26
3.A. Case1: Nanoshell 26
3.B. Case2: Nanosphere 31
3.C. Cellular S-values 36
4. Discussion 38
5. Conclusions 41

Chapter III. Nanoparticle Enhanced External Photon Therapy 43
Abstract 43
1. Introduction 44
1.A. Nanoparticle-Mediated Radiosensitization 44
1.B. Local Effect Model 46
1.C. Optical Diffraction Tomography 48
2. Material and Methods 50
2.A. Theoretical Modeling 50
2.A.a. Monte Carlo Simulation 50
2.A.b. Effect Modeling 55
2.A.c. Input Parameters 58
2.B. Biological Experiments 63
2.B.a. Cell and Gold Nanoparticles 63
2.B.b. Inductively Coupled Plasma - Atomic Emission Spectroscopy 63
2.B.c. Clonogenic Survival Assays 63
2.B.d. Western Blot Analysis 63
2.C. Imaging of Gold Nanoparticles 65
2.C.a. Transmission Electron Microscopy 65
2.C.b. Optical Diffraction Tomography 65

3. Results 66
3.A. Radial Dose distribution 66
3.B. Effect Modeling 70
3.B.a. Case 1 – Cell Shapes 70
3.B.b. Case 2 – Shifted Nucleus 72
3.B.c. Case 3 – GNP Sizes 80
3.B.d. Case 4 – 6 MV Beams 82
3.C. GNP Uptake and Cellular Toxicity 84
3.D. Clonogenic Survival Assay 84
3.E. Apoptosis and DNA damage 86
3.F. Localization of GNPs 88
3.G. GNP Radiosensitization Modeling 94
4. Discussion 98
5. Conclusions 107

Discussion 108

Conclusions 110

References 111
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dc.formatapplication/pdf-
dc.format.extent4345775 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subject방사선-
dc.subject방사선치료-
dc.subject나노입자-
dc.subject몬테카를로 시뮬레이션-
dc.subject방사선감수성 증강-
dc.subject생물학적 모델링-
dc.subject.ddc620.5-
dc.titleMonte Carlo Simulations and Experiments of Metal Nanoparticle Enhanced Low-Energy Radiotherapy-
dc.title.alternative금속나노입자 저에너지 방사선치료를 위한 몬테카를로 시뮬레이션과 실험-
dc.typeThesis-
dc.contributor.AlternativeAuthorWonmo Sung-
dc.description.degreeDoctor-
dc.contributor.affiliation융합과학기술대학원 융합과학부-
dc.date.awarded2018-02-
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