Tumor reactive singlet oxygen approach for Monte Carlo modeling of photodynamic therapy dosimetry

摘要

Photodynamic therapy (PDT) is an emergent technique used for the treatment of several diseases. It requires the interaction of three components: a photosensitizer, a light source and tissue oxygen. Knowledge of the biophysical aspects of PDT is important for improving dosimetry protocols and treatment planning. In this paper we propose a model to simulate the spatial and temporal distribution of ground state oxygen (O-3(2)), cumulative singlet excited state oxygen (O-1(2))(rx) and photosensitizer, in this case protoporphyrin IX (PpIX) in an ALA mediated PDT treatment. The results are analyzed in order to improve the treatment dosimetry. We compute the light fluence in the tissue using Monte Carlo simulations running in a GPU system. The concentration of O-3(2), (O-1(2))(rx) and the photosensitizer are calculated using this light fluence and a set of differential equations describing the photochemical reactions involved in PDT. In the model the initial photosensitizer concentration depends on tissue depth and type, moreover we consider blood vessel damage and its effect in the ground state oxygen concentration in the tissue. We introduce the tumor reactive single oxygen (TRSO) as a new dosimetry metric. It represents the amount of singlet oxygen per tumor volume that reacts, during the treatment, with the molecules in the tumor. This quantity integrates the effect of the light irradiance, the optical properties of the tumor and the normal tissue, the oxygen consumption and supply, and the photosensitizer biodistribution on the skin. (C) 2016 Elsevier B.V. All rights reserved.