Photodynamic Therapy (PDT) is a promising modality for cancer treatment. Typically, a laser is used to photo-excite a photosensitizer (PS) that subsequently collides with oxygen molecules promoting them to the metastable singlet delta state O2(1?). Singlet oxygen molecules are believed to be the species that destroys cancerous cells during PDT. Despite the benefit of targeted PDT that kills tumors selectively with minimum effect on surrounding healthy tissues, at the present time it is difficult, if not impossible, to predict the response of an individual to PDT. This has inhibited the acceptance of PDT for clinical uses. In this Phase II SBIR, Physical Sciences Inc. (PSI) proposes to extend the successful Phase I results and develop a 2D imaging sensor for PS fluorescence and singlet oxygen luminescence. Under previous NCI SBIR funding, PSI has developed, early prototype, in vivo capable dosimeters for PDT. These devices required pulsed lasers and temporally gated detectors. The overall goal of our proposed program is to produce an integrated, imaging PDT dosimeter that will enable real-time feedback to control PDT light dose during the treatment. In Phase I, we demonstrated a newly introduced 2D, near infrared imaging camera and obtained simultaneous in-vivo images of singlet oxygen and the photosensitizer. Based on the Phase I results, we have developed a strategy for singlet oxygen and photosensitizer dosimetry that can be used with conventional, continuous wave (cw) PDT excitation sources. In Phase II the combined PDT system will be designed, built, and extensively tested for performance verification by in vitro and in vivo studies. These studies will be completed in collaboration with Dartmouth College, our Phase I and Phase II partner. An accurate dosimeter to optimize the individual treatment response of PDT is necessary to improve the outcomes of PDT in a clinical environment. A fully developed instrument will be a valuable tool, first for PDT researchers and subsequently for clinical PDT uses.
The proposed research has the potential to significantly improve clinical PDT applications and outcomes. Real-time feedback of the distributions of PS and singlet oxygen during treatment will be a valuable tool for PDT researchers and clinicians. There is a long standing need for PDT dosimetry. A successful Phase II program will resolve this unmet need. Eventually, it could lead to much higher efficacy in PDT treatments in the clinic by enabling physicians to intelligently adapt individual light doses for PDT to match the different responses of individual patients.
