Physiological considerations acting on triplet oxygen for explicit dosimetry in photodynamic therapy.

The aims of this study were to determine the spatial and temporal theoretical distribution of the concentrations of Protoporphyrin IX, 3O2 and doses of 1O2. The type II mechanism and explicit dosimetry in photodynamic therapy were used. Furthermore, the mechanism of respiration and cellular metabolism acting on 3O2 were taken into account. The dermis was considered as an absorbing and a scattering medium. An analytical solution was used for light diffusion in the skin. The photophysical, photochemical and biological effects caused by PDT with the initial irradiances of 20, 60 and 150mW/cm2 were studied for a time of exposure of 20min and a maximum depth of 0.5cm. We found that the initial irradiance triples its value in 0.02cm and that almost 100% of PpIX is part of the dynamics of reactions in photodynamic therapy. Additionally, with about 40µMof 3O2 there is a balance between the consumed and supplied oxygen. Finally, we determined that with 60mW/cm2, the highest dose of 1O2 is obtained.

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 ß. 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 ß 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.