Near-Infrared Fluorescence Probes for Fluorescence-Guided Surgery: Current Clinical Probes and Emerging Candidates

Fluorescence-guided surgery (FGS) enables real-time visualization of tumor margins and microscopic residual lesions, thereby improving the completeness and precision of tumor resection. Paralleling these clinical advancements, fluorescence probes have shown significant progress in intraoperative imaging applications. Several probes approved by the U.S. Food and Drug Administration (FDA), including indocyanine green (ICG), 5-aminolevulinic acid (5-ALA), sodium fluorescein, methylene blue (MB), pafolacianine (OTL-38), and pegulicianine (LUM015), have been widely used in various solid tumor surgeries, while Akalux received approval in Japan in 2020 for near-infrared photoimmunotherapy. Beyond these established agents, a large number of novel probes are currently undergoing clinical evaluation, with design trends shifting toward active targeting and microenvironment responsiveness. This review provides an overview of FDA-approved probes and systematically summarizes representative probes in phase I-III clinical trials, focusing on their imaging mechanisms, clinical evidence, and translational challenges.