Real-Time Photosensitizer Dosimetry for Photodynamic Therapy

Photodynamic therapy (PDT) is a promising cancer treatment modality, but outcomes can be inconsistent due to variations in photosensitizer uptake and light dose delivery. Previous studies have demonstrated a 4/8-channel PDT dose dosimetry system capable of simultaneous light fluence and photosensitizer fluorescence measurements during pleural PDT treatments. An empirical optical property correction method was developed using Monte Carlo simulations and phantom experiments to enable quantitative in vivo photosensitizer concentration determination. The system was used to measure Photofrin concentrations at multiple sites in 20 patients undergoing pleural PDT clinical trial. Results showed large intra-and inter-patient heterogeneity in local Photofrin concentrations, with up to 3.1-fold differences within patients and 9.8fold differences between patients, despite standardized administration. This led to significant variations in delivered PDT dose. To enable real-time photosensitizer dosimetry during treatment, we have developed and validated an automated data analysis system that processes fluorescence and light fluence measurements on-the-fly. The system incorporates optical property correction and single value decomposition (SVD) fitting algorithms to calculate photosensitizer concentrations in real-time. Initial validation using phantom studies and clinical data simulation demonstrated good agreement between realtime and post-treatment analysis results, with concentration differences typically within 10%. The system features an 8channel simultaneous measurement capability and a user interface displaying instantaneous photosensitizer levels and cumulative PDT dose as treatment progresses. This real-time dosimetry approach could enable adaptive PDT where treatment is adjusted based on ongoing measurements, potentially improving consistency of outcomes. Further workflow testing and protocol standardization will be conducted before clinical implementation.