Diffused Optical Tomography using Oxygen-sensitive Luminescent Contrast Agent for

DESCRIPTION (provided by applicant): Molecule specific targeting and improving image contrast have been recognized as important research areas in cancer imaging. Goal of cancer diagnosis and prognosis research is to develop new imaging techniques to detect lesions with certainty in early stages so that they can be treated. Developing biomarkers, which will signal the presence and the type of lesion is a major thrust area in cancer imaging. Special emphasis is on developing biomarkers, which will predict the development of invasive and non-invasive cancer after treatment. In this work, we will focus on detecting and imaging hypoxic breast cancer using near-infrared (NIR) based diffused optical tomography (DOT) technique. Image contrast will be improved by using contrast agents targeting specific cancer cells involved with vasculature growth. Persisting hypoxia in a growing tumor can cause changes in the cells leading to aggressive cancer phenotype. Hypoxia driven progression often leads to local invasive growth, perifocal tumor cell spreading and distant cell tumor spreading. Similarly resistance to radiation and other treatments may become enhanced. Hence, it is necessary to monitor deep tissue hypoxic cancers, distinguish them from non-cancer specific hypoxia (i.e., due to physical injury etc.,) using a non-invasive imaging technique. Radiation Monitoring Devices, Inc (RMD) in collaboration with Dr. Raoul Kopelman from University of Michigan, will develop a near infrared (NIR) diffused optical tomography (DOT) instrument for breast cancer detection using peptide based luminescent contrast agent. The proposed contrast agent will target endothelial cells lining the vasculature or breast cancer cells. It will be localized within tumor and its luminescence intensity and lifetime will be oxygen- sensitive. Because poor oxygenation (hypoxia), which is a common feature of locally advanced solid tumors, can be utilized as a biomarker, the proposed contrast agent will provide an efficient way to monitor cancerous tumors. In addition, to advance the sensitivity of existing DOT instruments and take advantage of this new family of dyes, improvements to the optical system are proposed which includes use of sensitive Geiger mode avalanche detectors (GPD) and use of correlation technique. Demonstrating three-dimensional optical imaging using fluorescent lifetime tomography with a suitable contrast agent will provide a baseline for the performance of the Phase II prototype.