Intraoperative Fluorescent Image Guidance for Nerve-Sparing Prostatectomy: A Review of Historical Context and Current Research

Fluorescent probes in the near-infrared (NIR) range have immense potential to improve observation of positive margins, lymph nodes, and nerves in prostatectomy. Development of fluorescent dyes and mechanisms of cellular uptake paved the way for the current emerging technologies. However, intracellular transport of fluorophores proved to be logistically challenging with respect to intraoperative deployment. Peptide-based probes with high specificity for nerves enabled broader and more rapid labeling. Key features of the ideal probe include selectivity, minimal background noise, safety, and low cost. Human neuropeptide 401 (HNP401) and oxazine-based probes perform well in these categories. As for tumor-specific labeling, prostate specific membrane antigen is relatively selective for the prostate and can be conjugated to a fluorophore. NIR spectrum emission is an ideal range for clinical imaging use, as fluorescence occurs outside the field of visible light, and tissue optical properties diverge significantly at the visible-NIR transition. Indocyanine, carbocyanine, and fluorescein derivatives are common fluorophore conjugates for the probes. Finally, to harness the power of fluorescence intraoperatively, the surgeon must look through a specialized lens. Multiphoton microscopy, optical coherence tomography, and confocal laser endomicroscopy have emerged as frontrunners in this arena. As with any evolving technology, ongoing research is expanding the applications of fluorescent intraoperative imaging in prostate surgery. Innovations in camera technology, dye selection, and image processing are refining the technique's capabilities. A core challenge of these technologies translating into the operating room relates to size and the ability to view objects at vastly different magnifications. Dual modality zoom settings are promising solutions. Furthermore, interdisciplinary collaboration between surgeons, imaging specialists, and researchers continues to drive advancements. In conclusion, fluorescent intraoperative imaging has the potential to usher in a new era of precision and safety in prostate surgery.