title: Investigating the impact of oxygen concentration and blood flow variation on photodynamic therapy.
abstract: Type II photodynamic therapy (PDT) is used for cancer treatment based on the combined action of a photosensitizer, a special wavelength of light, oxygen (3O2) and generation of singlet oxygen (1O2). Intra-patient and inter-patient variability of oxygen concentration ([3O2]) before and after the treatment as well as photosensitizer concentration and hemodynamic parameters such as blood flow during PDT has been reported. Simulation of these variations is valuable, as it would be a means for the rapid assessment of treatment effect. A mathematical model has been previously developed to incorporate the diffusion equation for light transport in tissue and the macroscopic kinetic equations for simulation of [3O2], photosensitizers in ground and triplet states and concentration of the reacted singlet oxygen ([1O2]rx) during PDT. In this study, the finite-element based calculation of the macroscopic kinetic equations is done for 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH)-mediated PDT by incorporating the information of the photosensitizer photochemical parameters as well as the tissue optical properties, photosensitizer concentration, initial oxygen concentration ([3O2]0), blood flow changes andϕthat have been measured in mice bearing radiation-induced fibrosarcoma (RIF) tumors. Then, [1O2]rxcalculated by using the measured [3O2] during the PDT is compared with [1O2]rxcalculated based on the simulated [3O2]; both calculations showed a reasonably good agreement. Moreover, the impacts of the blood flow changes and [3O2]0on [1O2]rxhave been investigated, which showed no pronounced effect of the blood flow changes on the long-term1O2generation. When [3O2]0becomes limiting, small changes in [3O2] have large effects on [1O2]rx.
authors.affiliation: Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Rozhin
authors.initials: R
authors.lastname: Penjweini
authors.affiliation: Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jarod C
authors.initials: JC
authors.lastname: Finlay
authors.affiliation: Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Zhu
keywords: PDT; blood flow changes; in vivo mice models; macroscopic simulation; singlet oxygen generation; tissue oxygenation