Explicit dosimetry for photodynamic therapy: macroscopic singlet oxygen modeling

Singlet oxygen (O-1(2)) 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 O-1(2) concentration", [O-1(2)](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" [O-1(2)](rx,sd), it is feasible to determine the model parameters by fitting the computed [O-1(2)](rx) to the Photofrin-mediated PDT-induced necrotic distance using interstitially-measured Photofrin concentration and optical properties within each mouse. After determining the model parameters and the [O-1(2)](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 [O-1(2)](rx), because it takes into account the oxygen consumption (or light fluence 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. [GRAPHICS] Fitting computed [O-1(2)](rx) profile to the (symbol with std.) observed for 9 mice. The gray area indicates the range of the apparent threshold dose