Fluorescence Image-Guided Surgery - a Perspective on Contrast Agent Development

Abstract

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

Keywords: clinical development; clinical trial; contrast agent; fluorescence; fluorescence imaging system; image-guided surgery; near-infrared fluorescence.

Figure 1.

A pie chart of novel FGS contrast agent currently undergoing clinical translation split by probe type. The number of each agent type is listed next to the type.

Figure 2.

A pie chart highlighting the clinical trial phase of the novel FGS contrast agents currently undergoing clinical translation. The number of agents in each phase is listed.

Figure 3.. A.

Fluorescence excitation and emission wavelengths and B. imaging channel distribution of all fluorophores utilized by all novel FGS contrast agents undergoing clinical translation. The number of probes using each fluorophore are listed next to their names and the number of fluorophores in each channel are listed as well as the percentage of the total that number represents.

Figure 4.

A pie chart highlighting the broad clinical indication of the novel FGS contrast agents currently undergoing clinical translation. The number of agents targeted for each indication is listed next to it.