In situ PEDSy and light delivery platform for Intracavitory Photodynamic Therapy

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This translational project will develop, evaluate, and clinically test an integrated PDT Explicit Dosimetry System (PEDSy) and light delivery platform for quantitative measurement and delivery of photodynamic therapy (PDT) dose with feedback control. The system will include two key components: hardware for in situ PDT dosimetry and light source tracking in real-time, and software for treatment monitoring of light distribution throughout the pleural cavity during PDT of pleural-involving malignancy. The hardware is composed of a multi-channel instrument that can be used in the clinic during PDT to measure PDT dose generated by the PDT treatment light using the explicit dosimetry of light fluence rate and photosensitizer concentration. Here, the immediate clinical translation is to monitor the PDT dose at multiple sites in patients undergoing pleural PDT for mesothelioma, which has shown significant clinical efficacy in clinical trials to date. Fiber-optic-based fluorescence and diffuse reflectance spectra will also be collected at the same locations to calculate the tissue optical property correction factors for photosensitizer drug concentration. An IR navigation system and a 3D scanner will be developed to track the light source position in real-time as well as determining the geometrical shape of pleural surface for PDT treatment in real-time. The software is composed of a GPU-based Monte Carlo simulation for light fluence rate distribution on the entire pleural cavity coupled with estimation of the PDT dose distribution along the pleural cavity. The outcome of this project will be a novel hardware-software device, PEDSy, that has been optimized and rigorously validated under clinically-relevant conditions. We hypothesize that quantitative modeling of PDT dose deposition by PEDSy will be significantly more predictive of treatment outcome than the current method that employs measurements of light dose without incorporating photosensitizer uptakes. Innovation thereby stems from our unique goal to build a translatable platform for PDT dosimetry that is based on spatial modeling of comprehensive PDT dose, suitable for even sophisticated clinical applications of PDT, and yet generalizable to disease at other anatomic sites, such as head and neck and skin cancers. Moreover, we conceive that this integrated system for clinical PDT can be commercialized shortly after the end of development, and will provide real-time feedback to clinicians for personalization of treatment. Thus, this advanced instrument system is significant because it will open the pathway to dosimetry-based real time individualization of PDT that fully accounts for light and photosensitizer distributions. Lastly, our preliminary data indicate in situ measurements of PDT dose to be a more robust dose metric than the currently used approach which only incorporates light dose deposition. Our proposed platform is thereby expected to impact PDT dosimetry by building a platform that is based on a stronger dose metric (PDT dose) as well as by basing this modeling on its spatial distribution.