Photodynamic Therapy (PDT) is a promising modality for cancer treatment. Oxygen molecules in the metastable singlet delta state O2(1?) 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. Under NCI SBIR funding, Physical Sciences Inc. (PSI) has developed two prototype, in vivo capable dosimeters for PDT: a non-imaging ultra- sensitive photomultiplier tube (PMT)-based point sensor for singlet O2 detection and a 2D imaging sensor for PS fluorescence and singlet O2 detections. These devices use spectral and temporal discrimination methods to optimize sensitivity. The overall goal of our proposed program is to produce an integrated, imaging PDT system that will use real-time feedback to control PDT light dose during the treatment. In Phase I, we will develop and test a newly introduced 2D imaging camera that incorporates gating below a microsecond and a fast framing rate. This will enhance the sensitivity singlet oxygen by at least an order of magnitude. The system will be based upon PSI's current system platform of the 2D imaging system that has demonstrated the ability to observe singlet O2 and PS fluorescence in vivo produced during PDT. The current system uses a near infrared (NIR) sensitive camera for singlet O2 images. However, this camera does not have a fast time-gating capability, and that limits the detection method to only spectral discrimination. The system will be developed and tested on in vitro samples at PSI then transported to Dartmouth College for in vivo testing. The Phase I study result will be utilized to design a Phase II system for both PDT treatments and dosimeters. A fiber-coupled pulsed diode laser will be used for the PDT excitation source. The goal of the Phase I study is to demonstrate the detection sensitivity of the newly introduced 2D camera integrated in the PSI detection system. In Phase II the combined PDT system will be designed, built, and tested for extensive performance verification for in vitro and in vivo studies. 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 by concurrently operating PDT treatment and dosimeter as a combined system. 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.
