Monte Carlo Simulations and Experiments of Metal Nanoparticle Enhanced Low-Energy Radiotherapy

Abstract

The goal of radiation therapy is to deliver therapeutic doses to tumors while sparing surrounding normal tissue. Even though various techniques such as intensity-modulated radiation therapy (IMRT) have been introduced, increasing the therapeutic ratio is still a challenging goal in radiation cancer treatment. Over the last decade, the radiosensitizing potential of nanoparticles (NPs) has shown great promise. Interests in this field have particularly focus on gold nanoparticles (GNPs) due to its biocompatibility and high atomic number. However, macroscopic radiation dose calculations by mass energy absorption fail to predict observed experimental findings on level of radiosensitization and GNP concentrations. The purpose of this dissertation is to investigate whether dose inhomogeneities induced by GNPs on a cellular scale is a source of GNPs mediated radiosensitization. First, the feasibility of nanoparticle-enhanced Auger therapy was evaluated regarding electron energy spectra, microscopic dose distributions, and biological effectiveness using the S-value. Second, for nanoparticle-enhanced external photon therapy, biological effectiveness was systemically assessed in the various cell and nucleus geometry with GNPs. Radiation dose dependence of cell survival with GNPs was observed experimentally and predicted theoretically. The realistic modeling with 3D distributions of GNPs in live cells was established as observed by optical diffraction tomography (ODT). We performed Monte Carlo simulations to characterize interactions between GNPs and low-energy photons at the nanometer scale. Calculated radiation dose was applied to a biological model to quantify the GNP radiosensitization. Due to a steep radial dose falloff within short distances from the GNPs (<1% of the surface dose at 100 nm), geometric parameters such as the shape, size, and location of the cell, nucleus, and GNPs are important to assess GNP enhanced radiation therapy. GNP – Local Effect Model was established based on live cell images and showed good agreement with observed radiation response in the presence of GNPs.