Tackling physics challenges of conformal small animal image guided radiotherapy

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Functionalized nanoparticles have shown promise as a suitable cancer imaging contrast agent as well as therapeutic agent. However, the potential for nanoparticle use in combination with radiotherapy has not been fully examined and has been primarily investigated by means of cancer cell studies. Cell studies have demonstrated that radiation delivered in the presence of nanoparticles was more effective in killing cancer cells than radiotherapy alone. While this important finding could potentially result in improved treatment outcomes with reduced side effects, before radiotherapy with nanoparticles can be considered for clinical trials, its effects in small animals must first be investigated.***I propose to develop a unique small animal radiotherapy system capable of accurate radiation delivery under nanoparticle image guidance using a novel x-ray imaging technique, which will enable rigorous studies of nanoparticle-based radiotherapy of cancer.***1) I will design equipment and develop procedures assuring accurate radiotherapy delivery with conformal small animal irradiators. Devices for conformal small animal radiotherapy have been developed in recent years but their calibration procedure has not been developed. By means of detailed computer simulations and systematic experiments conducted at numerous institutions around the world, I will design hardware and software to assure accurate radiotherapy that mimics clinical radiotherapy as closely as possible.***2) I will design a novel small animal x-ray imaging system for visualization of nanoparticles and I will integrate it with a conformal small animal irradiator. I will use computer simulations to optimize x-ray fluorescence computed tomography (XFCT) imaging that shows promise in imaging nanoparticles in low concentrations, but has never been used for small animal studies due to the long imaging times. I will decrease imaging times by adding detectors and by developing more sophisticated data acquisition and image reconstruction techniques. I will test the optimized XFCT system on an experimental tabletop system before integrating it on a conformal small animal irradiator. Imaging experiments with test objects of different sizes and with different nanoparticles will be performed in both the simulation and experimental phases.***Upon successful completion of the proposed research, I will have built a unique radiotherapy system that will enable small animal studies of nanoparticle-based cancer radiotherapy. The system will be available to scientists in Canada and around the world and it will become an invaluable tool for translation of nanoparticle-based cancer therapy into the clinic. Moreover, I will provide highly qualified personnel by training MSc- and PhD-level students, who will become experts in radiation physics and who will be valuable assets for Canadian cancer centres and medical device engineering companies.********