Purpose: To model the amount of total reacted reactive oxygen species([ROS]ᵣₓ) and PDT dose based on explicit measurements of light fluence rate, photosensitizer concentration and tissue blood flow, on various locations in pleural cavity of patient receiving Photofrin-mediated photodynamic therapy for malignant pleural mesothelioma.
Methods: PDT was performed on patient’s lung cavity after complete surgical debulking of malignant pleural mesothelioma tissues. Light fluence rates were measured on 8 sites inside the lung cavity using 8 isotropic detectors sutured on the pleural wall. 4 out of the 8 isotropic detectors were connected to 4 spectrometers through bifurcated fibers to simultaneously acquired Photofrin fluorescence excited by the 630nm treatment light. The measured fluorescence spectra were fitted using an SVD algorithm to separate the contribution of Photofrin from other spectral components including ambient room light and tissue autofluorescence. The fluorescence SVD amplitudes were then corrected for tissue optical properties effect and quantified for absolute in vivo Photofrin concentrations. Tissue blood flow was measured on 2 sites where Photofrin fluorescence measurements were performed, using diffuse correlation spectroscopy (DCS). 2 DCS contact probes were sutured adjacent to the 2 isotropic detectors and tissue blood flow measurements were performed using a separate 785nm long coherent laser concurrently. PDT dose was then computed based on measured light fluence rate and Photofrin concentration, and [ROS]ᵣₓ was computed using ROSED model based on the measured light fluence rate, Photofrin concentration and tissue blood flow. These two dosimetric quantities were then compared among 10 pPDT patients.
Results: The average PDT dose delivered to 40 sites on 10 patients is 614±202.6μMJcm⁻² and the average [ROS]ᵣₓ delivered to 18 sites on the same 10 patients is 0.59±0.25mM.
Conclusion: Large intra- and inter-patient variations in PDT dose and [ROS]ᵣₓ were observed although a constant 60Jcm⁻² light fluence was prescribed.
Funding Support, Disclosures, and Conflict of Interest: This work is supported by grants from the National Institute of Health (NIH) R01EB028778 and P01CA087971, and the Department Of Radiation Oncology of University of Pennsylvania.