Explicit dosimetry for photodynamic therapy: macroscopic singlet oxygen modeling

Abstract Singlet oxygen ( 1 O 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 1 O 2 concentration”, [ 1 O 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” [ 1 O 2 ] rx , sd , it is feasible to determine the model parameters by fitting the computed [ 1 O 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 [ 1 O 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 [ 1 O 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. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)