Repurposing the Clinical Approved Photosensitizer Hematoporphyrin for in Vivo Fluorescence Endomicroscopy

Accurate tumor detection and boundary delineation are crucial for effective management of gastrointestinal cancer. However, current methods like white light endoscopy (WLE) have limitations in precision, and existing fluorescent contrast agents suffer from rapid metabolism, limited tumor accumulation, and concerns regarding biological safety. In our study, we propose repurposing hematoporphyrin (HpD), a clinically approved photosensitizer for photodynamic therapy (PDT), as a potent fluorescent contrast agent for in vivo endomicroscopy. Our research represents the first demonstration of utilizing HpD fluorescence signals to provide valuable contrast for tissue microstructures over an extended period (50 scans). To address autofluorescence interference common in endomicroscopy, we developed an endomicroscopic fluorescence imaging system compatible with violet excitation, a crucial requirement for effective fluorescence imaging using hematoporphyrin. Our study showcased the effectiveness of the system in leveraging HpD's fluorescence for visualizing tissue microstructures, enabling clear differentiation between tumorous, inflammatory, and normal tissues based on unique texture patterns. The seamless integration of this system with PDT workflows allows for real-time tumor margin identification and treatment guidance through the same optical fiber bundle. This method not only serves as an effective supplement to WLE but also paves the way for more precise theranostics in tumor management.