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Photodynamic therapy (PDT) is a photochemistry based cytotoxic technique that imparts cellular damage via excitation of a photosensitizer with drug-specific wavelength of light. Previously we and other groups have shown the efficacy of photoacoustic imaging in predicting treatment response of vascular targeted photodynamic therapy. In this work we evaluate the efficacy of photoacoustic imaging to monitor cellular targeted photodynamic therapy and its role in predicting recurrence. The dose at the treatment site for I PDT is determined by three factors: photosensitizer (PS) concentration, oxygenation status and delivered light irradiance. Most of the FDA approved photosensitizers in their triplet-excited state generate cytotoxic species by reacting with the ground state oxygen that is available in the surrounding environment. Given the inter- and intra-subject variability in the uptake of the photosensitizer and the distribution of oxygen in the tumor, understanding the interplay between these dose parameters could aid in determining photodynamic therapy efficacy. Using various subcutaneous and orthotopic mouse models we demonstrate both oxygenation status of the tumor prior to the treatment and the change in oxygen saturation 48 hrs post treatment can predict efficacy of Aminolevulinic acid (ALA) based cellular PDT with <92% sensitivity and specificity. We further compare the predictive capability of photoacoustic imaging with the more predominantly used fluorescence imaging and immunohistochemistry techniques.
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