Comparison of PDT parameters for RIF and H460 tumor models during HPPH-mediated PDT.

Singlet oxygen (1O2) is the major cytotoxic species producing PDT effects, but it is difficult to monitor in vivo due to its short life time in real biological environments. Mathematical models are then useful to calculate 1O2 concentrations for PDT dosimetry. Our previously introduced macroscopic model has four PDT parameters: ξ, σ, β and g describing initial oxygen consumption rate, ratio of photobleaching to reaction between 1O2 and 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, threshold 1O2 dose ([1O2]rx,sd). These PDT parameters have been investigated for HPPH using radiation-induced fibrosarcoma (RIF) tumors in an in-vivo C3H 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-vivo studies 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. Initial in vivo HPPH 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.