A Detailed Monte Carlo and Measurement-Based Assessment of Gold Nanoparticle Dose Enhancement for Ir-192 HDR Brachytherapy, External Beam Radiation Therapy and Image Contrast Enhancement for Computed Tomography (CT) and Cone Beam CT

Radiation therapy has long been one of oncologists' most effective weapons to combat cancer. Advances in beam shaping and imaging-guided approaches have paved the way towards more effective forms of radiation therapy with fewer side effects experienced by cancer patients. However, innovative strategies which can localize the effects of ionizing radiation while minimizing damage to surrounding tissue by lowering the overall dosage are still needed. One promising strategy is the use of targeted gold nanoparticles to locally enhance radiation while also providing image contrast enhancement. The ultimate goal of this research project was to develop an optimized nanoparticle-based method for image enhancement and radiation sensitization. In order to accomplish this goal, four specific aims were pursued: (1) Computationally-aided design to predict and interpret the dose enhancing effects of gold nanoparticles both on the macroscopic and microscopic scale using accurate x-ray and radioactive source geometry with different sizes, concentrations and shapes of gold nanoparticles, (2) Experimental synthesis of different sizes and concentrations of radiation-enhancing gold nanoparticles and developing optimal experimental dose enhancement and image contrast enhancement measurement set-ups guided by Monte Carlo simulations, (3) Experimental characterization of the local radiation dose enhancement and image contrast enhancing effects due to different sizes and concentrations of gold nanoparticles, and (4) Experimental in vitro investigation of the radiobiological effects of gold nanoparticles. Three novel aspects of this project also distinguish it from previous studies of nanoparticle-enhanced radiation therapy. First, the theoretical gold nanoparticle dose enhancement at different therapeutic radiation therapy energies staring with Ir-192 and going up to 18 MV energy and for different imaging modalities (Computed Tomography and Cone Beam Computed Tomography), was rationally guided by Monte Carlo computer simulations, involving accurate radiation beam and radiation source set-ups, to determine the optimum nanoparticle size, concentration and surface area to volume ratio (on the nanometer scale) that maximizes X-ray interactions at these energy ranges both macroscopically and microscopically. Second, these simulations were utilized to guide the optimal gold nanoparticle (GNP) size and concentration to produce optimal dose enhancement experimentally and guide the experimental set-up for experiments involving both imaging and therapy enhancement, with the long-term goal of developing theranostic applications. Thirdly, in vitro cell studies were performed by irradiating C-33a cervical cancer cells, dosed with different concentrations of GNPs, with 18 MV energy to observe the enhanced radiobiological cell killing effects of GNPs with different doses of high energy radiation using a Trypan Blue assay. The key areas of focus of this project are medical physics and radiation oncology, and the secondary areas of focus are imaging and biomedical engineering.