title: 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.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ken Kang-Hsin
authors.initials: KK
authors.lastname: Wang
authors.forename: Jarod C
authors.initials: JC
authors.lastname: Finlay
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Busch
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hahn
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Zhu
mesh_terms: D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D004058:Diffusion; D005240:Feasibility Studies; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy / Q000378:metabolism; D007700:Kinetics; D008027:Light; D051379:Mice; D008809:Mice, Inbred C3H; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D009381:Neoplasms, Radiation-Induced / Q000188:drug therapy / Q000378:metabolism; D010101:Oxygen Consumption; D010778:Photochemotherapy / Q000379:methods*; D026082:Singlet Oxygen / Q000737:chemistry*
chemical_list: D026082:Singlet Oxygen