Parameter Determination for Singlet Oxygen Modeling of BPD-Mediated PDT

Photodynamic therapy (PDT) offers a cancer treatment modality capable of providing minimally invasive localized tumor necrosis. To accurately predict PDT treatment outcome based on pre-treatment patient specific parameters, an explicit dosimetry model is used to calculate apparent reacted ¹O₂ concentration ([¹O₂]_rx) at varied radial distances from the activating light source inserted into tumor tissue and apparent singlet oxygen threshold concentration for necrosis ([¹O₂]_{rx, sd}) for type-II PDT photosensitizers. Inputs into the model include a number of photosensitizer independent parameters as well as photosensitizer specific photochemical parameters ξ, σ, and β. To determine the specific photochemical parameters of benzoporphyrin derivative monoacid A (BPD), mice were treated with BPD-PDT with varied light source strengths and treatment times. All photosensitizer independent inputs were assessed pre-treatment and average necrotic radius in treated tissue was determined post-treatment. Using the explicit dosimetry model, BPD specific ξ, σ, and β photochemical parameters were determined which estimated necrotic radii similar to those observed in initial BPD-PDT treated mice using an optimization algorithm that minimizes the difference between the model and that of the measurements. Photochemical parameters for BPD are compared with those of other known photosensitizers, such as Photofrin. The determination of these BPD specific photochemical parameters provides necessary data for predictive treatment outcome in clinical BPD-PDT using the explicit dosimetry model.