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PDT Dose Parameters Impact Tumoricidal Durability and Cell Death Pathways in a 3D Ovarian Cancer Model

Authors

  • Imran Rizvi,

    1. Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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  • Sriram Anbil,

    1. Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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  • Nermina Alagic,

    1. Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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  • Jonathan P. Celli,

    1. Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
    2. Department of Physics, University of Massachusetts Boston, Boston, MA
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  • Lei Zak Zheng,

    1. Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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  • Akilan Palanisami,

    1. Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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  • Michael D. Glidden,

    1. Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
    2. Department of Physics, University of Massachusetts Boston, Boston, MA
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  • Brian W. Pogue,

    1. Thayer School of Engineering, Dartmouth College, Hanover, NH
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  • Tayyaba Hasan

    Corresponding author
    • Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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Corresponding author email: thasan@mgh.harvard.edu (Tayyaba Hasan)

Abstract

The successful implementation of photodynamic therapy (PDT)-based regimens depends on an improved understanding of the dosimetric and biological factors that govern therapeutic variability. Here, the kinetics of tumor destruction and regrowth are characterized by systematically varying benzoporphyrin derivative (BPD)-light combinations to achieve fixed PDT doses (M × J cm−2). Three endpoints were used to evaluate treatment response: (1) Viability evaluated every 24 h for 5 days post-PDT; (2) Photobleaching assessed immediately post-PDT; and (3) Caspase-3 activation determined 24 h post-PDT. The specific BPD-light parameters used to construct a given PDT dose significantly impact not only acute cytotoxic efficacy, but also treatment durability. For each dose, PDT with 0.25 μM BPD produces the most significant and sustained reduction in normalized viability compared to 1 and 10 μM BPD. Percent photobleaching correlates with normalized viability for a range of PDT doses achieved within BPD concentrations. To produce a cytotoxic response with 10 μM BPD that is comparable to 0.25 and 1 μM BPD a reduction in irradiance from 150 to 0.5 mW cm−2 is required. Activated caspase-3 does not correlate with normalized viability. The parameter-dependent durability of outcomes within fixed PDT doses provides opportunities for treatment customization and improved therapeutic planning.

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