Explicit dosimetry for photodynamic therapy: macroscopic singlet oxygen modeling.

Area of Science:

• Biophysics
• Photochemistry
• Medical Physics

Background:

• Singlet oxygen ((1)O(2)) is the primary cytotoxic agent in type-II photodynamic therapy (PDT).
• Accurate dosimetry is crucial for predicting PDT treatment efficacy.
• Existing dosimetry methods may not fully capture the complex interplay of factors influencing PDT outcomes.

Purpose of the Study:

• To propose and validate an empirical macroscopic model for calculating the apparent reacted singlet oxygen concentration, [(1)O(2)](rx), as a clinical dosimetry quantity for PDT.
• To introduce a fitting parameter, the apparent singlet oxygen threshold concentration, [(1)O(2)](rx, sd), to determine model parameters.
• To assess the predictive capability of the proposed dosimetry model for PDT treatment outcomes in vivo.

Main Methods:

• Development of a four-parameter macroscopic model integrating light diffusion and PDT kinetics equations.
• Application of the model in arbitrary clinical treatment geometries.
• Determination of model parameters by fitting computed [(1)O(2)](rx) to necrotic distance in a mouse model, using measured photosensitizer concentration and optical properties.
• Inclusion of oxygen consumption and light fluence rate effects in the dosimetry calculation.

Main Results:

• The proposed model successfully calculates the apparent reacted singlet oxygen concentration, [(1)O(2)](rx).
• Model parameters were determined by fitting computed [(1)O(2)](rx) to experimental necrotic distances in a mouse model.
• The apparent reacted singlet oxygen concentration, [(1)O(2)](rx), demonstrated a stronger correlation with PDT outcome than traditional absorbed energy-based PDT dose.

Conclusions:

• The developed empirical model provides a feasible dosimetry approach for type-II PDT.
• The model's ability to incorporate oxygen consumption and light conditions suggests it can be a better predictor of PDT outcomes.
• This dosimetry model holds promise for assessing and optimizing photodynamic therapy in clinical settings.