A Near-Infrared Fluorescent Molecular Probe Targeting FGFR toward Precise Imaging of Colorectal Cancer

Abstract Colorectal cancer (CRC) is among the leading causes of cancer-related deaths globally. While surgical resection remains the primary treatment, the inaccurate identification of tumor margins and the presence of undetectable occult metastases pose significant clinical challenges. Near-infrared (NIR) fluorescence guided surgery (FGS) presents a potential solution to these issues; however, currently available clinical probes suffer from insufficient targeting specificity and limited overall imaging performance. This study introduces a novel NIR fluorescent probe, E-PEG4-S0456, designed to target fibroblast growth factor receptor (FGFR) for precise imaging of CRC. This probe demonstrates excellent photophysical properties and a strong binding affinity to FGFR, allowing for long-term, high-contrast imaging of both primary and metastatic CRC lesions across various animal models, achieving high tumor-to-background ratios and favorable biosafety profiles. Given these advantages, E-PEG4-S0456 has been validated as a promising tool with the potential to advance NIR−FGS technology and enhance the precision of diagnosis and treatment for CRC.