Explicit dosimetry for photodynamic therapy: macroscopic singlet oxygen modeling

摘要

Singlet oxygen (~1O2) is the major cytotoxic agent responsible for cell killing for type-II photodynamic therapy (PDT). An empirical four-parameter macroscopic model is proposed to calculate the "apparent reacted ~1O2 concentration", [~1O2]_(rx), as a clinical PDT dosimetry quantity. This model incorporates light diffusion equation and a set of PDT kinetics equations, which can be applied in any clinical treatment geometry. We demonstrate that by introducing a fitting quantity "apparent singlet oxygen threshold concentration" [~1O2]_(rx,sd), it is feasible to determine the model parameters by fitting the computed [~1O2]_(rx) to the Photofrin-mediated PDT-in-duced necrotic distance using interstitially-measured Photofrin concentration and optical properties within each mouse. After determining the model parameters and the [~1O2]_(rx,sd), we expect to use this model as an explicit dosimetry to assess PDT treatment outcome for a specific photosensitizer in an in vivo environment. The results also provide evidence that the [~1O2]_(rx,sd), because it takes into account the oxygen consumption (or light flu-ence rate) effect, can be a better predictor of PDT outcome than the PDT dose defined as the energy absorbed by the photosensitizer, which is proportional to the product of photosensitizer concentration and light fluence.