Quantitative Fluorescence Imaging of Chemophototherapy Drug Pharmacokinetics Using Laparoscopic SFDI.

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 combined with chemotherapeutic like Doxorubicin (Dox) to enable light-triggered drug release and targeted tumor destruction. Here, we present the validation of a wide-field laparoscopic spatial frequency domain imaging (SFDI) system in an ovarian cancer model. The system allows quantitative fluorescence imaging to obtain absolute drug concentrations in vivo to obtain the absolute concentrations of PoP and Dox fluorescence by correcting for tissue absorption and scattering effects. Fluorescence imaging revealed a significant reduction (~25%, p < 0.001) in PoP concentration in tumor regions post-illumination, demonstrating PDT-mediated photobleaching. Next, the Dox release experiment showed an increase of ~13 µg/mL Dox concentration at the local site. The ability to quantify both PoP and Dox fluorescence concentrations with a laparoscopic system underscores its potential for intraoperative monitoring of CPT efficacy. These findings indicate wide-field laparoscopic SFDI as a promising tool for guiding minimally invasive PDT and targeted drug delivery in preclinical and future clinical settings.