The Woodruff School

SUMMARY

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 CT or 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 (GNP) 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 an antibody-conjugated nanoparticle to a specific tumor marker, the higher photon 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 kilo-voltage source, the fluorescence emitted by the gold atoms would allow one to localize and quantify the GNP concentration. The proposed work will have two main aims. First, in order to quantify the GNP-mediated dose enhancement on a nanometer scale, a computational model will be developed. In this model, the spectrum of secondary electrons emitted by gold and water under irradiation with different photon sources will be determined by Monte Carlo methods. Then, event-by-event Monte Carlo transport of these electrons will be used to calculate the resulting dose from a hypothetical nanoparticle of gold or water. The second aim is 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 gold nanoparticle-aided radiation therapy (GNRT), but also facilitate the use of GNPs as imaging agents for drug-delivery or other similar studies.

SUBJECT:	Ph.D. Proposal Presentation

BY:	Bernard Jones

TIME:	Wednesday, September 29, 2010, 4:00 p.m.

PLACE:	Boggs, 3-47

TITLE:	Development of Dosimetry and Imaging Techniques for Pre-Clinical Studies of Gold Nanoparticle-Aided Radiation Therapy

COMMITTEE:	Dr. Sang Hyun Cho, Chair (NRE/MP) Dr. Chris Wang (NRE/MP) Dr. Eric Elder (NRE/MP) Dr. John Oshinski (BME) Dr. Andrew Karellas (Univ. of Mass.)

SUMMARY 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 CT or 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 (GNP) 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 an antibody-conjugated nanoparticle to a specific tumor marker, the higher photon 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 kilo-voltage source, the fluorescence emitted by the gold atoms would allow one to localize and quantify the GNP concentration. The proposed work will have two main aims. First, in order to quantify the GNP-mediated dose enhancement on a nanometer scale, a computational model will be developed. In this model, the spectrum of secondary electrons emitted by gold and water under irradiation with different photon sources will be determined by Monte Carlo methods. Then, event-by-event Monte Carlo transport of these electrons will be used to calculate the resulting dose from a hypothetical nanoparticle of gold or water. The second aim is 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 gold nanoparticle-aided radiation therapy (GNRT), but also facilitate the use of GNPs as imaging agents for drug-delivery or other similar studies.