Program in Biomedical Radiation Sciences, Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Radiat Res. 2021 Mar 1;195(3):293-300. doi: 10.1667/RADE-20-00223.1.
Numerous studies have strongly supported the application of gold nanoparticles (GNPs) as radio-enhanced agents. In our previous study, the local effect model (LEM I) was adopted to predict the cell survival for MDA-MB-231 cells exposed to 150 kVp X rays after 500 µg/ml GNPs treatment. However, microdosimetric quantities could not be obtained, which were correlated with biological effects on cells. Thus, we developed microdosimetric kinetic model (MKM) for GNP radio-enhancement (GNP-MKM), which uses the microdosimetric quantities such as dose-mean lineal energy with subcellular domain size. Using the Monte Carlo simulation tool Geant4, we estimated the dose-mean lineal energy with secondary radiations from GNPs and absorbed dose in the nucleus. The variations in MKM parameters for different domain sizes, and GNP concentrations, were calculated to compare the survival fractions predicted by both models. With a domain radius of 500 nm and a threshold dose of 20 Gy, the sensitizer enhancement ratio predicted by GNP-MKM and GNP-LEM was 1.41 and 1.29, respectively. The GNP-MKM predictions were much more strongly dependent on the domain size than were the GNP-LEM on the threshold dose. These findings provide another method to predict survival fraction for the GNP radio-enhancement.
许多研究强烈支持将金纳米粒子 (GNPs) 用作放射增强剂。在我们之前的研究中，采用局部效应模型 (LEM I) 预测了 MDA-MB-231 细胞在 150 kVp X 射线照射后暴露于 500 µg/ml GNPs 处理下的细胞存活率。然而，无法获得与细胞生物学效应相关的微剂量学数量。因此，我们开发了用于 GNP 放射增强的微剂量动力学模型 (GNP-MKM)，该模型使用了微剂量学数量，如带有亚细胞域大小的剂量平均线性能量。使用蒙特卡罗模拟工具 Geant4，我们估计了来自 GNPs 的次级辐射的剂量平均线性能量和核内吸收剂量。计算了不同域大小和 GNP 浓度下 MKM 参数的变化，以比较两种模型预测的存活分数。对于 500nm 的域半径和 20Gy 的阈值剂量，GNP-MKM 和 GNP-LEM 预测的敏化剂增强比分别为 1.41 和 1.29。GNP-MKM 的预测结果对域大小的依赖性比 GNP-LEM 对阈值剂量的依赖性更强。这些发现为 GNP 放射增强的存活分数预测提供了另一种方法。
