Core C: In vivo Imaging, Dosimetry and Sensing of Photodynamic-Immune Responses and Synergies

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ABSTRACT The central goal of the core to service the projects with measurement tools that they can use to control the individualization of treatment, and while they may be imperfect markers, they can provide guidance as to the optimal way to have synergistic combination treatments. The individual physiologic variation in immune response and PDT are both known to be at least as variable as responses from traditional broadband therapies such as surgery, chemotherapy or radiation. This core develops technologies and imaging tools that provide either direct measurement of dosimetry or surrogate biomarkers of response that would have clinical translation potential. These tools will be able to help: i) control PDT dosimetry; ii) sample for physio-biologic tissue responses, and iii) predict for synergy between PDT and immunotherapies. The work with Project 1 in dermatology focuses on Imaging PDT dosimetry by measuring the 3 core parameters of PDT, including: (i) oxygen, (ii) photosensitizer, and (iii) light, and surrogates and combinations of these. Imaging Oxygen from inherent PpIX delayed fluorescence was demonstrated here the first time. This tool will be optimized and developed into a controlled handheld tool for experimental deployment in the clinic. PpIX dosimetry innovation has advanced to allow cellphone measurement of levels, and is deployed at all clinics with low cost and high usability. Immune invasion and response imaging are exceptionally hard to visualize, but tools to provide surrogates of this are explored. In Project 2, pancreatic adenocarcinoma PDT and PDP Response Imaging is continued with analysis of CT scans and Endoscopic Ultrasound (EUS). Established studies of tissue stiffness mapping with EUS elastography and CT changes are used and imaging surrogate biomarkers of PDP effect by Radiomics has been completed, and a Radiomic index hypothesized. In Project 3, preclinical tissue stiffness & collagen mapping in situ are developed by UV fluorescence imaging of fresh tissue. This system will be used to iteratively determine how PDP changes in PDAC can be related to the definition of a quantitative Radiomic index. The Core develops tools for these projects and provides guidance on technology innovation and development as these are iterated on.