Author: Theresa Busch, Robert H Hadfield, Madelyn Johnson, Baozhu Lu, Hongjing Sun, Brian C. Wilson, Weibing Yang, Timothy C. Zhu 👨🔬
Affiliation: University of Glasgow, University of Toronto, University of Pennsylvania 🌍
Purpose: Direct detection of singlet-state oxygen (¹O₂) is crucial for advancing type II photodynamic therapy (PDT), but its short lifetime makes in vivo measurement highly challenging. Although Photofrin is a widely used photosensitizer in clinical practice, direct detection of its singlet oxygen signal has not yet been reported. Our cost-effective and user-friendly Multispectral Singlet Oxygen Dosimetry (MSOLD) system enables real-time, in vivo detection of ¹O₂ during Photofrin-mediated PDT. This advancement offers a more direct and accurate dosimetry method, potentially enhancing PDT outcomes by improving treatment precision and efficacy.
Methods: Mice with RIF tumors were treated with a 630 nm laser to excite Photofrin (5 mg/kg) at a power density of 150 mW/cm². Measurements were performed 24 hours post-injection. A total of 10 mice were included in the study. Real-time ¹O₂ spectra were recorded over 900 seconds using an Avantes spectrometer in high-sensitivity mode, coupled with a 1.5 mm optical fiber. The raw spectra underwent correction and smoothing, followed by the extraction of the singlet oxygen signal using a singular value decomposition (SVD) algorithm. Ground-state oxygen, photosensitizer concentrations, and fluence rates were measured to calculate singlet oxygen explicit dosimetry (SOED) for comparison. Tumor sizes were monitored for two weeks after treatment.
Results: Strong singlet oxygen spectra were successfully collected over 900 seconds from all mice. The singlet oxygen signal was effectively extracted using the Singular Value Decomposition (SVD) algorithm. A significant linear correlation was observed between the ¹O₂ signals measured with the MSOLD system and the SOED results, with both methods demonstrating reliable predictions of PDT treatment outcomes.
Conclusion: The MSOLD system provides an effective and non-invasive method for real-time monitoring of singlet oxygen during PDT, showing strong agreement with SOED results. This technique has the potential to improve PDT treatment planning and evaluation by offering accurate, real-time dosimetry.