Development of dosimetry and imaging techniques for pre-clinical studies of gold nanoparticle-aided radiation therapy

Cancer is one of the leading causes of death worldwide, and affects roughly 1.5 million new people in the United States every year. One of the leading tools in the detection and treatment of cancer is radiation. Tumors can be detected and identified using computed tomography (CT) or positron emission tomography (PET) scans, and can then be treated with external beam radiotherapy or brachytherapy. By taking advantage of the physical properties of gold and the biological properties of nanoparticles, gold nanoparticles (GNPs) can be used to improve both cancer radiotherapy and imaging. By infusing a tumor with GNPs, either using passive extravasation of nanoparticles by the tumor vasculature or active targeting of antibody-conjugated nanoparticles to a specific tumor marker, the higher photon interaction cross-section of gold will cause more radiation dose to be deposited in the tumor during photon-based radiotherapy. In principle, this would allow escalation of dose to the tumor while not increasing the dose to normal healthy tissue. Additionally, if a tumor infused with GNPs was irradiated by an external kilovoltage source, the fluorescence emitted by the gold atoms would allow one to localize and quantify the GNP concentration.;This work had two main aims: to quantify the GNP-mediated dose enhancement during gold nanoparticle-aided radiation therapy (GNRT) on a nanometer scale, and to develop a refined imaging modality capable of quantifying GNP location and concentration within a small-animal-sized object. In order to quantify the GNP-mediated dose enhancement on a nanometer scale, a computational model was developed. This model combines both large-scale and small-scale calculations in order to accurately determine the heterogeneous dose enhancement pattern due to GNPs. The secondary electron spectra were calculated using a condensed history Monte Carlo code, which is able to accurately take into account changes in beam quality throughout the tumor and calculate the average energy spectrum of the secondary charged particles created. Then, the dose distributions due to these electron spectra were calculated on a nanometer scale using an event-by-event Monte Carlo code.;The second aim was to develop an imaging system capable of reconstructing a tomographic image of GNP location and concentration in a small animal-sized object by capturing gold fluorescence photons emitted during irradiation of the object by an external beam. This would not only allow for localization of GNPs during GNRT, but also facilitate the use of GNPs as imaging agents for drug-delivery or other similar studies. It has been shown that a benchtop system utilizing a pencil beam of polychromatic x-rays is capable of generating this kind of image. In theory, using a cone-beam x-ray source would allow for extensive parallelization of data collection and decreasing scanning time. Thus, the specific aim of the current study was to develop a cone-beam implementation of x-ray fluorescence computed tomography (XFCT) that meets realistic constrains on image resolution, detection limit, scan time, and dose. A Monte Carlo model of this imaging geometry was developed and used to test the methods of data acquisition and image reconstruction. The results of this study were then used to drive the production of a functioning benchtop, polychromatic cone-beam XFCT system.