Explicit dosimetry for photodynamic therapy: macroscopic singlet oxygen modeling.
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.
Wang
Ken Kang-Hsin
KK
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Finlay
Jarod C
JC
Busch
Theresa M
TM
Hahn
Stephen M
SM
Zhu
Timothy C
TC
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*
D026082:Singlet Oxygen