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RISS 인기검색어
- 검색키워드
- 저자 : Schuemann, J (검색결과 3 건)
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Dependence of gold nanoparticle radiosensitization on cell geometry
Sung, W.,Ye, S. J.,McNamara, A.,McMahon, S.,Hainfeld, J.,Shin, J.,Smilowitz, H.,Paganetti, H.,Schuemann, J. Royal Society of Chemistry 2017 Nanoscale Vol.9 No.18
<P>The radiosensitization effect of gold nanoparticles (GNPs) has been demonstrated both in vitro and in vivo in radiation therapy. The purpose of this study was to systematically assess the biological effectiveness of GNPs distributed in the extracellular media for realistic cell geometries. TOPAS-nBio simulations were used to determine the nanometre-scale radial dose distributions around the GNPs, which were subsequently used to predict the radiation dose response of cells surrounded by GNPs. MDA-MB-231 human breast cancer cells and F-98 rat glioma cells were used as models to assess different cell geometries by changing (1) the cell shape, (2) the nucleus location within the cell, (3) the size of GNPs, and (4) the photon energy. The results show that the sensitivity enhancement ratio (SER) was increased up to a factor of 1.2 when the location of the nucleus is close to the cell membrane for elliptical-shaped cells. Heat-maps of damage-likelihoods show that most of the lethal events occur in the regions of the nuclei closest to the membrane, potentially causing highly clustered damage patterns. The effect of the GNP size on radiosensitization was limited when the GNPs were located outside the cell. The improved modelling of the cell geometry was shown to be crucial because the dose enhancement caused by GNPs falls off rapidly with distance from the GNPs. We conclude that radiosensitization can be achieved for kV photons even without cellular uptake of GNPs when the nucleus is shifted towards the cell membrane. Furthermore, damage was found to concentrate in a small region of the nucleus in close proximity to the extracellular, GNP-laden region.</P>
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Underwood, T S A,Sung, W,McFadden, C H,McMahon, S J,Hall, D C,McNamara, A L,Paganetti, H,Sawakuchi, G O,Schuemann, J IOP 2017 Physics in medicine & biology Vol.62 No.8
<P>Whilst Monte Carlo (MC) simulations of proton energy deposition have been well-validated at the macroscopic level, their microscopic validation remains lacking. Equally, no gold-standard yet exists for experimental metrology of individual proton tracks. In this work we compare the distributions of stochastic proton interactions simulated using the TOPAS-nBio MC platform against confocal microscope data for Al<SUB>2</SUB>O<SUB>3</SUB>:C,Mg fluorescent nuclear track detectors (FNTDs). We irradiated <img ALIGN='MIDDLE' ALT='$8\times 4\times 0.5$ ' SRC='http://ej.iop.org/images/0031-9155/62/8/3237/pmbaa6429ieqn001.gif'/> mm<SUP>3</SUP> FNTD chips inside a water phantom, positioned at seven positions along a pristine proton Bragg peak with a range in water of 12 cm. MC simulations were implemented in two stages: (1) using TOPAS to model the beam properties within a water phantom and (2) using TOPAS-nBio with Geant4-DNA physics to score particle interactions through a water surrogate of Al<SUB>2</SUB>O<SUB>3</SUB>:C,Mg. The measured median track integrated brightness (IB) was observed to be strongly correlated to both (i) voxelized track-averaged linear energy transfer (LET) and (ii) frequency mean microdosimetric lineal energy, <img ALIGN='MIDDLE' ALT='$\overline{{{y}_{F}}}$ ' SRC='http://ej.iop.org/images/0031-9155/62/8/3237/pmbaa6429ieqn002.gif'/>, both simulated in pure water. Histograms of FNTD track IB were compared against TOPAS-nBio histograms of the number of terminal electrons per proton, scored in water with mass-density scaled to mimic Al<SUB>2</SUB>O<SUB>3</SUB>:C,Mg. Trends between exposure depths observed in TOPAS-nBio simulations were experimentally replicated in the study of FNTD track IB. Our results represent an important first step towards the experimental validation of MC simulations on the sub-cellular scale and suggest that FNTDs can enable experimental study of the microdosimetric properties of individual proton tracks.</P>
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