A Singlet Molecular Oxygen Imaging Sensor for Photodynamic Therapy

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 tumors, pretreated with the photosensitizer, 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 cancerous cells during PDT. In this Phase I proposal Physical Sciences Inc. (PSI) proposes to develop an optically-based monitor that will image the spatial extent and location of both the photosensitizer and singlet oxygen emission. The system will build upon our recent results that have demonstrated the ability to observe singlet oxygen optical emission in-vivo produced during PDT. The system will use a fiber coupled, pulsed diode laser and a state of the art, just commercially introduced 2-D imaging camera to develop and demonstrate spatial imaging of photosensitizer concentration and singlet oxygen production during PDT. The system will be developed and tested on in-vitro samples at PSI then transported to Dartmouth College for in-vivo testing in collaboration with our Phase I partners. The goal of these tests is to demonstrate that the Phase I imaging device can map the spatial location of the singlet oxygen production within the tumors and correlate it with the spatial distribution of the photosensitizer. In Phase II we will design, build, and test a portable, ruggedized instrument through extensive tests both at Dartmouth College and the Massachusetts General Hospital. 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, correlating photosensitizer concentrations with singlet oxygen production, and discerning mechanisms of tumor necrosis. to public health. 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 will be a valuable research tool to develop new, more effective treatments.