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Parameter determination for BPD mediated vascularPDT.

Michele M Kim1, Baochang Liu2, Joann Miller2

  • 1Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104 ; Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, PA 19104.

Proceedings of Spie--The International Society for Optical Engineering
|May 23, 2015
PubMed
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The drug-light interval (DLI) influences benzoporphyrin derivative monoacid ring A (BPD) cell killing mechanisms in photodynamic therapy (PDT). This study quanties photochemical parameters for BPD-PDT with a 15-minute DLI, crucial for predicting clinical outcomes.

Area of Science:

  • Photochemistry
  • Oncology
  • Biomedical Engineering

Background:

  • Benzoporphyrin derivative monoacid ring A (BPD) photodynamic therapy (PDT) induces cell death via apoptosis or vascular damage, contingent on the drug-light interval (DLI).
  • A 3-hour DLI results in necrosis secondary to tumor cell damage, whereas a 15-minute DLI leads to necrosis from treatment-induced vascular damage.

Purpose of the Study:

  • To investigate if distinct cell death mechanisms in BPD-mediated PDT influence photochemical parameters within a macroscopic singlet oxygen model.
  • To determine photochemical parameters (ξ, σ, β, γ) and the threshold singlet oxygen dose for BPD-PDT using a 15-minute DLI.

Main Methods:

  • Murine fibrosarcoma (RIF) model was utilized to evaluate BPD-PDT efficacy.
  • Mice received BPD (1 mg/kg) with a 15-minute DLI, followed by 690nm light at varying fluence rates (12-150 mW/cm²) and total fluences (24-135 J/cm²).

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  • Tumor necrosis was assessed 24 hours post-PDT via H&E staining to determine photochemical parameters and in-vivo BPD concentration (0.05-0.30 μM).

    • Main Results:

    • The study successfully determined four photochemical parameters (ξ, σ, β, γ) and the threshold singlet oxygen dose for BPD-PDT with a 15-minute DLI.
    • In-vivo BPD concentrations were quantified, ranging from 0.05-0.30 μM.
    • Photochemical parameters derived from the 15-minute DLI will be compared with those from a 3-hour DLI.

    Conclusions:

    • The determined photochemical parameters for BPD-PDT with a 15-minute DLI provide essential data for predicting treatment outcomes in clinical settings.
    • Understanding the impact of different cell death mechanisms on photochemical parameters is crucial for optimizing PDT protocols.