Department of Radiation Oncology, Division of Medical Physics and Biophysics, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
Phys Med Biol. 2012 Oct 21;57(20):6371-80. doi: 10.1088/0031-9155/57/20/6371. Epub 2012 Sep 21.
Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries for people over the age of 50. In this work, the dosimetric feasibility of using gold nanoparticles (AuNP) as radiosensitizers to enhance kilovoltage stereotactic radiosurgery for neovascular AMD is investigated. Microdosimetry calculations at the sub-cellular level were carried out to estimate the radiation dose enhancement to individual nuclei in neovascular AMD endothelial cells (nDEF) due to photon-induced photo-/Auger electrons from x-ray-irradiated AuNP. The nDEF represents the ratio of radiation doses to the endothelial cell nuclei with and without AuNP. The calculations were carried out for a range of feasible AuNP local concentrations using the clinically applicable 100 kVp x-ray beam parameters employed by a commercially available x-ray therapy system. The results revealed nDEF values of 1.30-3.26 for the investigated concentration range of 1-7 mg g(-1), respectively. In comparison, for the same concentration range, nDEF values of 1.32-3.40, 1.31-3.33, 1.29-3.19, 1.28-3.12 were calculated for 80, 90, 110 and 120 kVp x-rays, respectively. Meanwhile, calculations as a function of distance from the AuNP showed that the dose enhancement, for 100 kVp, is markedly confined to the targeted neovascular AMD endothelial cells where AuNP are localized. These findings provide impetus for considering the application of AuNP to enhance therapeutic efficacy during stereotactic radiosurgery for neovascular AMD.
年龄相关性黄斑变性（AMD）是 50 岁以上发达国家人群失明的主要原因。在这项工作中，研究了使用金纳米颗粒（AuNP）作为增敏剂来增强用于新生血管性 AMD 的千伏立体定向放射外科的剂量学可行性。在亚细胞水平进行微剂量学计算，以估计由于 x 射线照射的 AuNP 产生的光/俄歇电子，在新生血管性 AMD 内皮细胞（nDEF）中的各个核的辐射剂量增强。nDEF 表示有和没有 AuNP 时内皮细胞核的辐射剂量比。使用商业可用的 X 射线治疗系统中使用的临床可行的 100 kVp X 射线束参数，针对可行的 AuNP 局部浓度范围进行了计算。结果表明，在所研究的浓度范围为 1-7 mg g(-1) 时，nDEF 值分别为 1.30-3.26。相比之下，对于相同的浓度范围，分别计算了 80、90、110 和 120 kVp X 射线的 nDEF 值为 1.32-3.40、1.31-3.33、1.29-3.19 和 1.28-3.12。同时，作为距离 AuNP 的函数的计算表明，对于 100 kVp，增强的剂量明显局限于 AuNP 定位的靶向新生血管性 AMD 内皮细胞。这些发现为考虑在立体定向放射外科治疗新生血管性 AMD 期间应用 AuNP 来增强治疗效果提供了动力。
