title: Comparison of PDT parameters for RIF and H460 tumor models during HPPH-mediated PDT.
abstract: Singlet oxygen (1O2) is the major cytotoxic species producing PDT effects, but it is difficult to monitorin vivodue to its short life time in real biological environments. Mathematical models are then useful to calculate1O2concentrations for PDT dosimetry. Our previously introduced macroscopic model has four PDT parameters:ξ,σ,βand g describing initial oxygen consumption rate, ratio of photobleaching to reaction between1O2and cellular targets, ratio of triplet state (T) phosphorescence to reaction between T and oxygen (3O2), and oxygen supply rate to tissue, respectively. In addition, the model calculates a fifth parameter, threshold1O2dose ([1O2]rx,sd). These PDT parameters have been investigated for HPPH using radiation-induced fibrosarcoma (RIF) tumors in anin-vivoC3H mouse model. In recent studies, we additionally investigated these parameters in human non-small cell lung carcinoma (H460) tumor xenografts, also using HPPH-mediated PDT.In-vivostudies are performed with nude female mice with H460 tumors grown intradermally on their right shoulders. HPPH (0.25 mg/kg) is injected i.v. at 24 hours prior to light delivery. Initialin vivoHPPH concentration is quantified via interstitial HPPH fluorescence measurements after correction for tissue optical properties. Light is delivered by a linear source at various light doses (12-50 J/cm) with powers ranging from 12 to 150 mW per cm length. The necrosis radius is quantified using ScanScope after tumor sectioning and hematoxylin and eosin (H&E) staining. The macroscopic optimization model is used to fit the results and generate four PDT parameters. Initial results of the parameters for H460 tumors will be reported and compared with those for the RIF tumor.
authors.affiliation: Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Baochang
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
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.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Gallagher-Colombo
authors.affiliation: Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Busch
authors.affiliation: Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Zhu
keywords: H460 tumor; HPPH; Photodynamic therapy; RIF tumor; dosimetry; macroscopic model; singlet oxygen