Current trends and key considerations in the clinical translation of targeted fluorescent probes for intraoperative navigation

The rapid development of fluorescence imaging for intraoperative navigation has spurred further development of targeted fluorescent probes in the past decade. Only a few nontargeted dyes, including indocyanine green and methylene blue, are currently applied for fluorescence guided surgery in the clinic. While no targeted fluorescent probes have been approved for the clinic, a number of them have entered clinical trials. These probes have emission wavelengths in the visible and near infrared (NIR)-I (700-900 nm) range. Among them, activatable probes and nanoprobes have generated special interest. Compared with NIR-I fluorescent probes, NIR-II (1000-1700 nm) fluorescent probes exhibit better intravital performance in terms of increased penetration depths, reduced tissue autofluorescence, and higher signal-to-background ratios. However, more challenges are expected before the successful translation of NIR-II probes from bench to bedside. This review provides a brief overview of targeted fluorescent probes under clinical evaluation and recent achievements in the field of NIR-II fluorescence imaging. In addition, we outline key considerations concerning the design of fluorescent probes for clinical translation.