Translational contrast agents for use in fluorescence image-guided tumor surgery

Currently, surgical intervention remains the foundation in curing most solid tumors. Over the past few decades, even with rapid intraoperative tissue pathology assessment, the overall rate of positive surgical margins for tumors stagnated between 15 % and 60 %. The increased local recurrence rates and poor prognoses associated with various cancers, such as head and neck, brain, breast, lung, prostate, and gastrointestinal cancers, are linked to positive margins. Recently, driven by the concept of precise surgery, significant advancements have been reported in the intraoperative use of fluorescent contrast agents in the field of surgery. Molecular imaging via intraoperative fluorescence plays a guiding role in surgery, providing surgeons with visible fluorescent images. In clinical applications, fluorescent contrast agents can clearly delineate tumor boundaries, offering high recognition capacities and real-time guidance during surgery. Additionally, they can localize lymph node metastases, detect small metastatic lesions, and identify critical anatomical structures during surgery, thus reducing the risk of collateral damage. An ideal surgical guidance technology should lack radiation and display a high sensitivity and good resolution and an adjustable field of view, with rapid imaging. Enhancing the tissue penetration of fluorescence and targeting capacities of molecular probes are critical in providing more comprehensive tumor-related data. Additionally, screening and identifying other tumor biomarkers and more of their corresponding targeted molecular data are essential in enhancing the specificity of molecular imaging. Finally, the investigation and use of a wider range of near-infrared fluorescent dyes with improved biocompatibilities and imaging are critical in designing synthetic probes for application in intraoperative navigation. The development of novel, efficient, safe fluorescent contrast agents is a critical direction in current pharmaceutical research and development.