Phantom-to-in vivo Correlation of Tsold, Msold, and Soed for Quantitative Singlet Oxygen Dosimetry In Photodynamic Therapy
Abstract
Purpose
Time-resolved singlet oxygen luminescence detection (TSOLD) enables direct measurement of singlet oxygen generation during photodynamic therapy (PDT), while multispectral SOLD (MSOLD) and singlet oxygen explicit dosimetry (SOED) provide complementary cumulative and model-based dose metrics. This work aims to establish a controlled phantom-to-in vivo correlation framework linking TSOLD, MSOLD, and SOED dosimetry methods for quantitative singlet oxygen monitoring in PDT.
Methods
A free-space photon-counting TSOLD system employing a nanosecond pulsed diode laser, reflective fiber probe, 1270-nm filtering, an ID230 InGaAs SPAD, and a Swabian Time Tagger was validated in Rose Bengal phantoms. Measurements were performed in water, liquid intralipid, and solid agarose scattering phantoms with varying photosensitizer concentration and optical properties. Decay curves were fit using the standard singlet oxygen kinetic model to extract signal amplitude and lifetime metrics. Building on this validation and recent in vivo benzoporphyrin derivative (BPD) feasibility studies, upcoming experiments will extend to Photofrin liquid and solid phantoms to directly compare TSOLD decay-derived metrics, MSOLD cumulative luminescence, and SOED-modeled reacted singlet oxygen dose. The same multimodal correlation pipeline will then be translated into Photofrin-mediated murine tumor PDT studies to evaluate predictive dosimetry relationships in vivo.
Results
Rose Bengal phantom experiments demonstrated systematic scaling of TSOLD signal amplitude with concentration and significant scattering-induced modifications of apparent singlet oxygen lifetime, highlighting the importance of optical transport effects in tissue-like media. In vivo BPD studies further confirmed feasibility of photon-counting singlet oxygen detection in murine tumors, motivating extension toward multimodal dosimetry correlation.
Conclusion
A standardized phantom-to-mouse framework integrating TSOLD, MSOLD, and SOED will enable cross-validation of singlet oxygen dosimetry methods and support future translation of quantitative PDT dose monitoring into preclinical and clinical applications.