A Self‐Calibrating Fluorescent‐Photoacoustic Integrated Probe Enables Fast Visualizing Pancreatic Cancer and Imaging‐Guided Tumor Surgery

Abstract Pancreatic cancer is known for its high invasiveness and metastasis, making rapid visualization and precise treatment critical for improving patient outcomes. Current diagnostic tools lack abilities to provide rapid and accurate tumor localization, particularly for real‐time intraoperative guidance. To address this gap, the study has developed a novel Förster Resonance Energy Transfer (FRET)‐mediated dual‐ratiometric near‐infrared fluorescence (NIRF)/photoacoustic (PA) bimodal probe, SiRho‐SHD‐NTR, specifically designed for the fast and accurate navigation of pancreatic tumor resection. The probe, due to its excellent binding affinity with nitroreductase (NTR), can rapidly reach response saturation. Cellular experiments demonstrate that the probe rapidly and efficiently penetrates cancer cells, enhancing the effectiveness of PA imaging for preliminary diagnosis and tumor localization, while also enabling the rapid visualization of pancreatic tumors through NIRF imaging. Leveraging the rapid response characteristics of the probe to NTR, the study achieves precise tumor imaging in orthotopic pancreatic cancer mice by spraying the probe, within ≈5 min. More importantly, the probe even allows for the fast visualization of metastatic tumors and fluorescence‐guided surgical resection. It is believed that SiRho‐SHD‐NTR will offer a promising method in the rapid visualization of pancreatic cancer and provide a powerful tool for imaging‐guided tumor surgery, targeting both primary and metastatic tumors.