PROJECT 4 : REAL-TIME OPTICAL DIAGNOSTICS OF TISSUE FOR PDT DOSIMETRY ANDTREATMENT CHARACTERIZATIONThe underlying premise of the proposed research is that clinical photodynamic therapy (PDT) dosimetry islimited, and that useful, minimally invasive optical instrumentation can be developed for in-situ dosimetry andtreatment assessment based on measurement of tissue optical properties, tissue hemoglobin and drugconcentration, tissue blood oxygen saturation and tissue blood perfusion. Over the past five years we havebuilt and validated new experimental tools for this purpose, and we began exploration of their potential inanimal models and human tissues during clinical PDT. Highlights of this work included the discovery ofpredictive correlations between PDT treatment efficacy, average blood oxygen saturation and blood flow inradiation induced fibrosarcoma (RIF) mouse tumor models. In addition we initiated optical propertymeasurements in the clinic during intraperitoneal (IP) surgery. Our new aims derive from this experience.We will upgrade our instrumentation for clinical and animal model measurements to gather moremacroscopic tissue information in-situ with greater speed and fidelity. More importantly, our scientificemphasis will shift to explore the potential of these tools to characterize tumor microenvironment broughtabout by biological targeting, and to develop dosimetric measures for PDT in animal models with and withoutbiological targeting (with Project 3); a byproduct of these studies will be correlation studies of macroscopicvariables with microscopic variables from immunohistochemistry. Finally, in collaboration with Projects 1 and5 we will assess dose heterogeneity, tissue hypoxia, and blood flow in human tissues (normal andcancerous) during ongoing human IP and pleural clinical trials. We anticipate this quantitative informationwill take us further towards rapid, minimally invasive, in-situ optical diagnostics for PDT.
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