Quantitative Fluorescence Imaging of Porphyrin Phospholipid Photobleaching and Light Activated Liposomal Doxorubicin Release Using Wide-field and Laparoscopic SFDI in an Ovarian Cancer Model

TL;DR

This study introduces a new imaging system to monitor cancer treatment combining light therapy and chemotherapy in real-time during surgery.

Contribution

A wide-field laparoscopic SFDI system is developed for quantitative fluorescence imaging of photobleaching and drug release in ovarian cancer.

Findings

The system enables accurate quantification of PoP photobleaching and Dox release in vivo.

Fluorescence imaging showed significant PoP reduction post-illumination, confirming PDT effects.

The system differentiates PoP and Dox fluorescence, supporting real-time monitoring of treatment efficacy.

Abstract

Chemophototherapy (CPT) is an emerging cancer treatment that leverages the synergistic effects of photodynamic therapy (PDT) and chemotherapy. This approach utilizes photosensitizers like Porphyrin Phospholipid (PoP) and Doxorubicin (Dox) to enable phototriggered drug release and targeted tumor destruction. In this study, we present the development and validation of a wide-field laparoscopic spatial frequency domain imaging (SFDI) system, designed to improve intraoperative quantitative fluorescence imaging and monitoring of PoP photobleaching, a PDT-driven effect for tumor destruction, and light-activated Dox release, which facilitates targeted chemotherapeutic drug delivery in an ovarian cancer model. Compared to previous flexible endoscopic imaging methods, our laparoscopic SFDI system offers enhanced spatial coverage, enabling accurate wide-field optical property quantification in minimally invasive surgical settings. Using this system, we performed quantitative fluorescence imaging in vivo to obtain absolute concentrations of PoP and Dox fluorescence, correcting for tissue absorption and scattering effects. This capability allows for precise assessment of PoP photobleaching and Dox release kinetics with improved spatial resolution. Fluorescence imaging revealed a significant reduction in PoP concentration in tumor regions post-illumination, demonstrating the PDT-mediated photobleaching effect and successful light-triggered drug release activation for chemo-induced tumor destruction. The ability to differentiate PoP and Dox fluorescence in a laparoscopic system underscores its potential for real-time intraoperative monitoring of CPT efficacy. These findings establish wide-field laparoscopic SFDI as a promising tool for guiding minimally invasive photodynamic therapy and targeted drug delivery in clinical settings.

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