Electron emission spectra from gold-nanoparticles for dose estimation in radiation therapy

放射治疗是癌症治疗的最常见方式之一。当辐射穿过细胞和组织时，它会储存能量并形成离子，从而导致癌细胞死亡。这种细胞毒性效应由初级粒子引发，甚至更多地由次级电子引发。由于电离过程不是细胞特异性的，并且对肿瘤和健康细胞都有损伤，因此将辐射吸收元素沉积到肿瘤中可以使其对辐射敏感，这有效地降低了对健康组织的剂量。 研究表明，使用金纳米粒子可以提高X射线[1]和质子束[2]的辐射剂量。由于纳米颗粒附近的陡峭剂量梯度，常规的宏观剂量测定不足以表征剂量分布。因此，需要蒙特卡罗轨道结构模拟来解释二次电子的局部纳米级相互作用[3]。这些模拟目前是基于简化的理论散射模型，这是不再有效的能量低于几千电子伏，导致外推具有很大的不确定性。在水（通常用作生物物质的替代品）的情况下，这些模型可以根据实验数据进行调整，以便模拟对微观应用有效[4]。然而，对于金，所需的原子散射截面无法通过实验获得，但来自金纳米颗粒的实验电子光谱可用于基准模拟数据，从而降低后续剂量计算的不确定性。最近报道了低keV能量的金纳米颗粒的测量电子光谱，其中与Geant 4 MC模拟的一致性较差[5]。为了解释治疗X射线能量下的局部剂量增强，研究光子能量下的电子发射是至关重要的，光子能量足以触发具有许多低能二次电子的大型俄歇级联。本研究的目的是测量不同粒径的金纳米粒子在X射线和质子束照射下发射电子的能谱。建议的X射线能量高于金L-边缘（12千电子伏），由同步加速器和临床X射线源产生。建议的质子能量为100 keV，这是布拉格峰内。该项目将获得重要的基础数据，以估计纳米金的剂量分布和剂量增强，从而促进此类放射增敏剂的临床应用。[1]J.F. Hainfeld等人，J. Pharm.，60，977 - 85（2008）。[2]J.C. Polf等人，应用物理学快报，98，3 - 5（2011）。[3]H.N. McQuaid等人，sci.代表：6，19442（2016）。[4]S. Incerti等人， 医学物理，37，4692 - 4708（2010）中描述的。[5]R. Casta等人，物理医学生物学，60，9095 - 9105（2015）。

Radiotherapy is one of the most common modalities for cancer treatment. As the radiation passes through cells and tissues, it deposits energy and forms ions which can result in cancer cell death. Such cytotoxic effects are initiated by the primary particle and even more by secondary electrons. Because ionizing processes are not cell specific and damage tumor and healthy cells alike, a deposition of radiation absorbing elements into the tumor can sensitize it to radiation, which effectively reduces the dose to healthy tissue. Studies have shown that the use of gold nanoparticles can produce a dose enhancement for irradiation with X-rays [1] and proton beams [2]. Due to the steep dose gradient in the vicinity of nanoparticles, conventional macroscopic dosimetry is insufficient for the characterization of dose distribution. Monte Carlo track structure simulations are therefore required to account for localized nanoscopic interactions of secondary electrons [3]. These simulations are currently based in simplified theoretical scattering models, which are no longer valid for energies below a few keV resulting in extrapolations with large uncertainties. In the case of water (often used as a substitute for biological matter), these models could be adjusted to experimental data so that the simulation is valid for microscopic applications [4]. For gold, however, the required atomic scattering cross sections cannot be obtained experimentally, but experimental electron spectra from gold nanoparticles can be used to benchmark the simulated data, and thus, reduce the uncertainty of subsequent dose calculations.Measured electron spectra from gold nanoparticles were recently reported for low keV energies, where the agreement with Geant4 MC simulation was poor [5]. To account for the localized dose-enhancement at therapeutic X-ray energies, it is crucial to investigate electron emission at photon energies sufficient to trigger a large Auger cascade with many low-energy secondary electrons. The energy loss and self-absorption of electrons within the gold nanoparticle should also be determined, in terms of the particle size.The resent proposal aims to measure energy spectra of electrons emitted from gold nanoparticles of different size for X-rays and proton beam irradiation. The proposed X-ray energies are above the gold L-edge (12 keV) and produced by a synchrotron and clinical X-ray sources. The proposed proton energy is 100 keV, which is within the Bragg-peak. The project will obtain important fundamental data to estimate the dose distribution and dose enhancement by gold nanoparticle and thereby promote the translation of such radiosensitizers into clinical applications.[1] J.F. Hainfeld et al., J. Pharm., 60, 977-85 (2008).[2] J.C. Polf et al., Appl. Phys. Lett., 98, 3-5 (2011).[3] H.N. McQuaid et al., Sci. Rep., 6, 19442 (2016).[4] S. Incerti et al., Med. Phys., 37, 4692-4708 (2010).[5] R. Casta et al., Phys. Med. Biol., 60, 9095-9105 (2015).