In the past several decades, a number of novel fluorescence image-guided surgery (FGS) contrast agents have been underdevelopment, with many in clinical translation and undergoing clinical trials. In this review, we have identified andsummarized the contrast agents currently undergoing clinical translation. In total, 39 novel FGS contrast agents are beingstudied in 85 clinical trials. Four FGS contrast agents are currently being studied in phase III clinical trials and are poisedto reach FDA approval within the next two to three years. Among all novel FGS contrast agents, a wide variety of probetypes, targeting mechanisms, and fluorescence properties exists. Clinically available FGS imaging systems have beendeveloped for FDA approved FGS contrast agents, and thus further clinical development is required to yield FGS imagingsystems tuned for the variety of contrast agents in the clinical pipeline. Additionally, study of current FGS contrast agentsfor additional disease types and development of anatomy specific contrast agents is required to provide surgeons FGStools for all surgical specialties and associated comorbidities. The work reviewed here represents a significant effort frommany groups and further development of this promising technology will have an enormous impact on surgical outcomesacross all specialties.
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