Evaluating Dose and Dose Enhancement Ratio Distributions at the Nano and Microscale: Towards Advancing Accuracy in Nanoparticle-Enhanced Radiotherapy

Abstract

This PhD thesis delves into the enhancement of radiation therapy through the integration of high-atomic-number (high-Z) nanoparticles (NPs) with synchrotron radiation. The use of high-Z NPs such as gold and gadolinium is investigated because of their potential to increase secondary electron production and enhance energy deposition within tumor tissues. This effect is particularly pronounced when photon energies in the kiloelectronvolt range are employed. A key focus of this research is the examination of dose heterogeneities introduced by NPs, which traditional metrics such as the Dose Enhancement Ratio (DER) often fail to capture. The thesis critiques the conventional use of average DER values, which do not adequately reflect the nanoscale and microscale dose distribution surrounding the nanoparticles. These average values overlook critical variations that could influence therapeutic outcomes. The findings of this thesis underscore the inadequacy of using average DER values. Moreover, the study pioneers a novel methodology for estimating the anisotropy of microdosimetric quantities around gold nanoparticles using Variance Reduction Techniques (VRTs) with Monte Carlo simulations. This approach enables the acquisition of detailed dosimetric data, extending to distances beyond one micrometer from the nanoparticle surface. This research pave the way for future research that could further enhance the precision and efficacy of cancer treatment protocols. These results advocate for a paradigm shift in the way dose distributions are analyzed and interpreted in the context of NP-enhanced radiotherapy.