Real Time, Automated Singlet Oxygen Dosimeter for PDT

DESCRIPTION (provided by applicant): Photodynamic therapy (PDT) is a relatively new, rapidly developing, and promising modality for cancer treatment. PDT uses certain compounds known as photosensitizers (PS's) that are preferentially retained in malignant tumors. With visible light, the photosensitizers initiate a reaction that selectively kills the malignant cells to which they are attached. FDA approval has been granted for treatment of esophageal and certain lung cancers. PDT is being used in clinical trials for bladder, brain, skin and other cancers. PDT is also being applied to important areas outside of cancer treatment including age related macular degeneration and actinic keratosis, a pre-cancerous skin condition. There is considerable evidence that singlet molecular oxygen (O2(a1?)) is the active species in cancer cell necrosis. A real-time dosimeter for singlet oxygen produced during PDT would be a valuable tool for better understanding the PDT process and for improving treatment outcomes. The overall objective of the proposed SBIR Fast Track program is to build upon our recent success in developing a prototype, real-time detector for singlet oxygen to complete focused, but extensive pre-clinical studies. In Phase I we will significantly improve the sensitivity of the sensor and quantitatively demonstrate these improvements in a series of in-vitro and in-vivo studies. In Phase II we will incorporate the lessons learned in Phase I and build an upgraded, fieldable version and deliver it to the Massachusetts General Hospital (MGH) for an extensive series of animal and human studies. One critical study will be to demonstrate the quantitative relationship between PDT treated tumor regression and the amount of singlet oxygen produced during the treatment. Carefully constructed protocols for the animal studies will examine important PDT parameters including PS type and concentration, light intensity and total dose, and the time between PS infusion and PDT treatment. These studies will use only FDA approved photosensitizers (ALA and BPD) to maximize the relevance of the results to PDT in humans. Near the end of the three year program, MGH will complete a study of PDT generated singlet oxygen from healthy human subjects with topical ALA on their skin. The Fast Track program will result in a robust and statistically significant data base that will be submitted to the FDA at the end of the program. The goal is to obtain FDA approval to market the singlet oxygen monitor to PDT researchers as the initial target market. This program will be relevant to an emerging form of cancer therapy and will provide validation of a real-time sensor that has the potential to improve PDT treatment outcomes. PDT is a growing and promising modality, and the results of this project will not only provide important data that could improve treatment outcomes, but also facilitate FDA approval of the device so it would be available to more researchers with the goal of advancing PDT.