Potential for enhancing external beam radiotherapy for lung cancer using high-Z nanoparticles administered via inhalation.
Potential for enhancing external beam radiotherapy for lung cancer using high-Z nanoparticles administered via inhalation.
复制标题
DOI：
10.1088/0031-9155/60/18/7035
复制
发表时间：
2015-09-21
影响因子：
3.5
通讯作者：
Ngwa W
中科院分区：
文献类型：
--
作者：
Hao Y;Altundal Y;Moreau M;Sajo E;Kumar R;Ngwa W
纳米粒子辅助放射治疗正在成为一种有前途的方法，通过高原子序数 (Z) 纳米粒子的放射增敏作用来增强放射治疗。然而，将足够有效浓度的此类纳米颗粒递送至肿瘤仍然是一个挑战。本研究调查了在外照射放射治疗期间通过吸入施用高 Z 纳米颗粒 (NP) 导致的肺部肿瘤剂量增强。这里研究的纳米颗粒包括：顺铂纳米颗粒（CNP）、卡铂纳米颗粒（CBNP）和金纳米颗粒（GNP）。使用蒙特卡罗生成的兆伏能谱，使用先前采用的分析方法来估计通过吸入途径（IR）施用的纳米颗粒与静脉（IV）施用相比，由于辐射诱导的光电子而对肺部肿瘤的剂量增强。先前的研究表明，FDA 批准的顺铂浓度中约有 5% 通过静脉注射到达肺部。同时，最近的实验研究表明，与 IV 相比，IR 可以到达肺部的 NP 浓度高出 3.5-14.6 倍。考虑到这些因素，针对一系列纳米颗粒浓度和肿瘤大小计算了剂量增强因子（DEF），定义为有纳米颗粒和没有纳米颗粒的放射治疗剂量之比。然后将 IR 的 DEF 与 IV 的 DEF 进行比较。对于浓度比 IV 高 3.5 倍的 IR 和直径为 2 cm 的肿瘤，CNP、CBNP 和 GNP 获得了高达 1.19、1.26 和 1.51 的具有临床意义的 DEF 值。作为比较，通过静脉注射获得了 1.06、1.08 和 1.15 的值。对于浓度高 14.6 倍的 IR，可以获得更高的 DEF 值，例如CNP 为 1.81。结果还表明，正如预期的那样，DEF 随着视野大小的增加或肿瘤体积的减小而增加。这项工作的结果表明，与外束放疗期间的静脉注射相比，靶向高Z CNPs/CBNPs/GNPs 的IR 注射可以使肺部肿瘤具有临床意义的DEF。对于 FDA 批准的 CNP 或 CBNP 浓度，这可以允许在同步放化疗期间通过光电机制对肿瘤进行额外的剂量增强。
Nanoparticle-aided radiation therapy is emerging as a promising modality to enhance radiotherapy via the radiosensitizing action of high atomic number (Z) nanoparticles. However, the delivery of sufficiently potent concentrations of such nanoparticles to the tumor remain a challenge. This study investigates the dose enhancement to lung tumors due to high-Z nanoparticles (NPs) administered via inhalation during external beam radiotherapy. Here NPs investigated include: cisplatin nanoparticles (CNPs), carboplatin nanoparticles (CBNPs), and gold nanoparticles (GNPs). Using Monte Carlo–generated megavoltage energy spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumors due to radiation-induced photoelectrons from the NPs administered via inhalation route (IR) in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung via IV. Meanwhile recent experimental studies indicate that 3.5–14.6 times higher concentrations of NPs can reach the lung by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the radiotherapy dose with and without nanoparticles was calculated for a range of NPs concentrations and tumor sizes. The DEF for IR was then compared with that for IV. For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of up to 1.19, 1.26, and 1.51 were obtained for CNPs, CBNPs and GNPs. In comparison values of 1.06, 1.08, and 1.15 were obtained via IV administration. For IR with 14.6 times higher concentrations, even higher DEF values were obtained e.g. 1.81 for CNPs. Results also showed that the DEF increased with increasing field size or decreasing tumor volume, as expected. The results of this work indicate that IR administration of targeted high-Z CNPs/CBNPs/GNPs could enable clinically significant DEF to lung tumors compared to IV administration during external beam radiotherapy. For FDA approved concentrations of CNPs or CBNPs considered, this could allow for additional dose enhancement to tumors via photoelectric mechanism during concomitant chemoradiotherapy.