Gold Nanoparticles Enhanced Diffuse Optical Imaging and Radiation Therapy

Cancer is a leading cause of morbidity and mortality in the United States and worldwide. Commonly used cancer treatment methods include surgery, chemotherapy, and Radiation therapy (RT), the last of which is used in about half of all treatments. Imaging plays an important role in cancer diagnosis and radiation treatment. Gold nanoparticles (GNP) can strongly absorb optical light and x-ray because of the surface plasmon resonance (SPR) effect of the nanoparticles and the high atomic number of the gold. Therefore, it has a great potential to enhance both optical imaging and radiation dose delivery. This dissertation includes: (1) the development of an optical imaging system using GNP as a contrast agent; (2) the development of a Monte Carlo simulation based treatment planning system (TPS) for a small animal irradiation system to establish a reliable dose calculation platform which is subsequently used in (3) a simulation study of radiation dose enhancement by GNP. In the imaging study, a SPR optical imaging (SPROI) system was developed. Gold nanorods (GNR) of various concentrations were successfully reconstructed from centimeter-scaled volumes in simulation, phantom and animal experiments. SPROI detected GNR at a concentration as low as 18 μg/mL, which is 3 orders more sensitive than regular x-ray imaging. To the best of our knowledge, this is one of the first studies that investigated transmission-based whole body diffuse optical tomography of centimeter- scaled small animals using GNR as contrast agents. In the TPS development, an EGSnrc/BEAMnrc model of our image-guided SMall Animal Arc Radiation Treatment (iSMAART) system was assembled and validated by dosimetric measurement. The results from BEAMnrc modeling and computed tomography (CT) mass density calibration were used in DOZXYZnrc to calculate three- dimensional dose distribution in the irradiated animal. The dose calculation was validated by a dosimeter implanted in the thorax of a mouse. Image guided radiation therapy was demonstrated on a mouse bearing breast tumor and one bearing prostate tumor. In the simulation study, a cylindrical phantom with a sphere inclusion was used to simulate a human breast bearing a tumor in the center. The sphere volume was loaded with 7 and 18 mg/g of GNP, respectively, to simulate the tumor uptake of GNP. Dose distributions were calculated in DOSXYZnrc with a kV and a MV irradiation source respectively, delivered through single or multiple beams. Dose enhancement in the tumor as well as sparing in the normal tissue behind the tumor were observed in the kV irradiations for both nanoparticle concentration groups. Compared to MV irradiation which showed almost no dose enhancement when GNP was used, GNP enhanced kV irradiation significantly increased the tumor-surface ratio while achieving a smaller penumbra and better dose uniformity inside the tumor region