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Photobleaching-based Dosimetry Predicts Deposited Dose in ALA-PpIX PDT of Rodent Esophagus

Authors

  • Chao Sheng,

    1. Thayer School of Engineering, Dartmouth College, Harvard Medical School, Boston, MA
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  • P. Jack Hoopes,

    1. Thayer School of Engineering, Dartmouth College, Harvard Medical School, Boston, MA
    2. Department of Surgery, Dartmouth Medical School, Harvard Medical School, Boston, MA
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  • Tayyaba Hasan,

    1. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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  • Brian W. Pogue

    Corresponding author
    1. Thayer School of Engineering, Dartmouth College, Harvard Medical School, Boston, MA
    2. Department of Surgery, Dartmouth Medical School, Harvard Medical School, Boston, MA
    3. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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*email: pogue@dartmouth.edu (Brian W. Pogue)

Abstract

An improved method to estimate dose to esophageal tissue was investigated in the setting of photodynamic therapy with aminolevulinic acid-induced protoporphyrin IX (PpIX) treatment. A model of treatment-induced edema in the esophagus mucosa proved to be a well controlled and useful way to test the dosimetry model, and the light from the treatment laser together with the PpIX fluorescence intensity could be quantified reliably in real time. Dosimetry calculations based upon the detected fluorescence and bleaching kinetics were used to calculate the “effective” dose to the tissue, and a correlation was shown to exist between this metric and the edema induced in the esophagus. The difference between animals with no detectable treatment effect and those with significant edema was predictable based upon the dose calculation. The underlying assumption in the interpretation of the data is that rapid photobleaching of PpIX occurs when there is ample oxygen supply, and this bleaching is not present when oxygen is limited. This leads to the prediction that integration of the light and drug dose, in intervals where appreciable photobleaching occurs, should provide a prediction of the relative dose of singlet oxygen produced. This detection system and rodent model can be used for prospective dosimetry studies that focus on optimization of esophageal PDT.

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