Monochromatic x-ray cancer phototherapy and characterization of the Compton Light Source

The Compton Light Source (CLS) promises to provide a compact source of high intensity, well-collimated, small spot size, hard x-rays with tunable monochromatic energy. By colliding relativistic electrons with picosecond photon bunches, x-rays are generated through inverse Compton scattering (ICS). The tunable energy range of these x-ray photons (10-120 keV) is well suited for diverse medical applications allowing work, which is now possible only at synchrotron sources, to take place in a clinical or local research setting. High quality images and better tumor control with lower dose on normal tissue may be achieved with x-rays tuned just above the k-edge characteristic energies of the contrast agents. This dissertation first considers design, initial beam alignment and x-ray detection efforts at the CLS. In particular, methods to characterize the system performance and to detect x-rays generated by inverse Compton scattering are discussed. Although a significant background bremsstrahlung field was produced during ICS x-ray generation, a small signal (∼9.1% above noise) of ICS x-rays was measured against the background during initial alignment efforts.;The dissertation then considers the in vitro evaluation of PC3 prostate cancer cells treated with radiosensitizing agents such as lohexol and tin protoporphyrin IX (SnPPIX) to demonstrate the dose enhancement effect under irradiation by both conventional and synchrotron x-ray sources. A dose enhancement factor at 10% cell survival (DEF10%) of 1.66 was measured for cells treated with lohexol at 14 mg/ml using a hardened conventional x-ray source. Synchrotron experiments at the Stanford Synchrotron Radiation Laboratory confirmed the predicted energy dependence of the dose enhancement factor for cells in solution with 28 mg/ml lohexol. The relationship between DEF10% and energy was experimentally determined for energies between 25 and 42 keV. Although irradiation below the k-edge of iodine showed only small dose enhancement (DEF10% of 1.16, 1.2 and 1.37 at 25, 28, and 32 keV, respectively), irradiation above the k-edge increased dose enhancement (DEF10% of 1.7, 2.12, and 2.24 at 33.4, 34, and 42 keV, respectively). Experiments with extracellular SnPPIX at a conventional x-rays source showed modest dose enhancement (DEF10%=1.17), but the inherent toxicity of SnPPIX precluded evaluation at distant synchrotron sources.