Singlet Molecular Imaging Sensor for Photodynamic Therapy (7218-060)

DESCRIPTION (provided by applicant): Photodynamic therapy (PDT) is a promising cancer treatment. PDT uses the affinity of photosensitizers such as hematoporphyrin derivative (HPD) and other compounds to be selectively retained in malignant tumors. When tum ors, pretreated with the photosensitizer (PS), are irradiated with visible light, a photochemical reaction occurs and tumor cells are destroyed. Oxygen molecules in the metastable singlet delta state O2(1 ) are believed to be the species that destroys canc erous cells during PDT. An optically- based imaging device that can visualize spatial maps of both the singlet oxygen production and the location of the PS in a tumor during PDT would be a valuable tool for PDT research and more effective treatments. In a Phase I program Physical Sciences Inc. (PSI) developed and demonstrated a 2D imaging system and successfully produced spatially resolved images of photosensitizers and singlet oxygen both in-vitro and in-vivo. The in-vivo images were from mice containing t umor models. Based on these successful Phase I results, in Phase II, PSI proposes to design, build and test a complete and ruggedized 2D imaging sensor for simultaneous, co-registered singlet oxygen emission and PS fluorescence. The system will use a fiber coupled diode laser for light irradiation and two CCD cameras with a spectral discrimination method. A novel, intensified, near-IR array camera will be used for the detection of singlet oxygen emission. The 2D spatially resolved image of singlet oxygen em ission will be correlated with PS fluorescence obtained with a visible imaging camera. The system will be tested on in-vitro photosensitizer samples at PSI. Comprehensive in-vivo tests will also be performed on tumor models in laboratory rats with our coll aborators at Dartmouth College. A fully developed instrument will be a valuable tool for several aspects of PDT research including: elucidating kinetic and physiological phenomena, assessing new photosensitizers targeted to specific tissue areas, correlati ng photosensitizer concentrations with singlet oxygen production, and evaluating the relationship between singlet oxygen production with tumor regression. PUBLIC HEALTH RELEVANCE: This project will demonstrate a novel diagnostic for improving the treatment of cancer by light activated cancer killing drugs. A successful program will produce high resolution images of the location of an excited form of oxygen (produced by the light activated drugs within tumors) that is responsible for killing the tumor. It wi ll be a valuable research tool to develop new, more effective treatments.