Refining Photochemical Dose–Response Modeling In Single-Fraction Photofrin-PDT Using [ROS]ₓ and Msold Correlation
Abstract
Purpose
To refine the photochemical dose–response relationship for single-fraction Photofrin-mediated PDT by relating modeled reacted singlet oxygen dose to long-term tumor control and by using multispectral singlet oxygen luminescence detection (MSOLD) as an independent cross-validation of singlet oxygen generation in vivo.
Methods
Tumor-bearing C3H mice with RIF tumors were treated with a 630 nm continuous-wave laser at a fixed fluence rate of 150 mW/cm². Total fluence was varied by illumination time to create different treatment groups (≈180–337 J/cm²). For each animal, in vivo Photofrin concentration was measured by fluorescence spectroscopy with SVD-based spectral decomposition and phantom correction, and intratumoral oxygenation was monitored using an OxyLite probe. These individualized physiological inputs were incorporated into the ROSED macroscopic photochemical model to estimate reacted singlet oxygen dose, [ROS]rx. Long-term outcome was assessed using Kaplan–Meier analysis and local control rate (LCR). In a subset of animals, MSOLD was performed during PDT to directly measure near-infrared luminescence near 1270 nm, providing cross-validation of singlet oxygen production during treatment.
Results
Across ~35 treated mice till date, LCR increased with increasing modeled [ROS]rx, showing a stronger monotonic trend than fluence alone. Group-level analysis demonstrated good correspondence between mean [ROS]rx and tumor control. MSOLD confirmed detectable singlet oxygen emission during illumination across all treatment groups. While instantaneous MSOLD signals showed substantial temporal variability, cumulative MSOLD increased monotonically with illumination time and exhibited group-dependent trends consistent with ROSED-based photochemical dose.
Conclusion
Combining individualized photochemical modeling with MSOLD cross-validation strengthens singlet oxygen–based interpretation of PDT response and provides a refined single-fraction baseline for predicting long-term control beyond fluence alone.