Sinha Neeharika, Cifter Gizem, Sajo Erno, Kumar Rajiv, Sridhar Srinivas, Nguyen Paul L, Cormack Robert A, Makrigiorgos G Mike, Ngwa Wilfred
Department of Sciences, Wentworth Institute of Technology, Boston, Massachusetts.
Department of Physics and Applied Physics, University of Massachusetts, Lowell, Massachusetts; Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Int J Radiat Oncol Biol Phys. 2015 Feb 1;91(2):385-92. doi: 10.1016/j.ijrobp.2014.10.001. Epub 2014 Dec 5.
Recent studies show promise that administering gold nanoparticles (GNP) to tumor cells during brachytherapy could significantly enhance radiation damage to the tumor. A new strategy proposed for sustained administration of the GNP in prostate tumors is to load them into routinely used brachytherapy spacers for customizable in situ release after implantation. This in silico study investigated the intratumor biodistribution and corresponding dose enhancement over time due to GNP released from such GNP-loaded brachytherapy spacers (GBS).
An experimentally determined intratumoral diffusion coefficient (D) for 10-nm nanoparticles was used to estimate D for other sizes by using the Stokes-Einstein equation. GNP concentration profiles, obtained using D, were then used to calculate the corresponding dose enhancement factor (DEF) for each tumor voxel, using dose painting-by-numbers approach, for times relevant to the considered brachytherapy sources' lifetimes. The investigation was carried out as a function of GNP size for the clinically applicable low-dose-rate brachytherapy sources iodine-125 (I-125), palladium-103 (Pd-103), and cesium-131 (Cs-131).
Results showed that dose enhancement to tumor voxels and subvolumes during brachytherapy can be customized by varying the size of GNP released or eluted from the GBS. For example, using a concentration of 7 mg/g GNP, significant DEF (>20%) could be achieved 5 mm from a GBS after 5, 12, 25, 46, 72, 120, and 195 days, respectively, for GNP sizes of 2, 5, 10, 20, 30, and 50 nm and for 80 nm when treating with I-125.
Analyses showed that using Cs-131 provides the highest dose enhancement to tumor voxels. However, given its relatively longer half-life, I-125 presents the most flexibility for customizing the dose enhancement as a function of GNP size. These findings provide a useful reference for further work toward development of potential new brachytherapy application with in situ dose painting administered via gold nanoparticle eluters for prostate cancer.
近期研究表明，在近距离放射治疗期间向肿瘤细胞施用金纳米颗粒（GNP）可显著增强对肿瘤的辐射损伤。为在前列腺肿瘤中持续施用GNP提出的一种新策略是将它们加载到常规使用的近距离放射治疗间隔物中，以便在植入后实现可定制的原位释放。这项计算机模拟研究调查了由于从这种负载GNP的近距离放射治疗间隔物（GBS）释放的GNP导致的肿瘤内生物分布以及随时间的相应剂量增强情况。
使用实验确定的10纳米纳米颗粒的肿瘤内扩散系数（D），通过斯托克斯 - 爱因斯坦方程估算其他尺寸的D。然后，使用得到的D的GNP浓度分布，采用数字剂量描绘方法，针对与所考虑的近距离放射治疗源寿命相关的时间，计算每个肿瘤体素的相应剂量增强因子（DEF）。该研究针对临床适用的低剂量率近距离放射治疗源碘 - 125（I - 125）、钯 - 103（Pd - 103）和铯 - 131（Cs - 131），作为GNP尺寸的函数进行。
结果表明，在近距离放射治疗期间，通过改变从GBS释放或洗脱的GNP的尺寸，可以定制对肿瘤体素和子体积的剂量增强。例如，使用7毫克/克的GNP浓度，对于2、5、10、20、30和50纳米尺寸的GNP以及用I - 125治疗时80纳米尺寸的GNP，分别在5、12、25、46、72、120和195天后，在距GBS 5毫米处可实现显著的DEF（>20%）。
分析表明，使用Cs - 131对肿瘤体素提供的剂量增强最高。然而鉴于其相对较长的半衰期，I - 125在根据GNP尺寸定制剂量增强方面具有最大的灵活性。这些发现为通过金纳米颗粒洗脱剂进行原位剂量描绘开发潜在的新近距离放射治疗应用的进一步工作提供了有用的参考。
