Na_V1.7 targeted fluorescence imaging agents for nerve identification during intraoperative procedures

Area of Science:

• Biomedical Engineering
• Surgical Innovation
• Neuroscience

Background:

• Iatrogenic nerve damage affects millions globally, with oncologic surgery posing increased risks due to anatomical distortions.
• Current surgical practice lacks effective contrast agents to precisely identify and protect vital peripheral nerves.
• Voltage-gated sodium channel 1.7 (Na_V1.7) is highly expressed in peripheral nerves, presenting a potential intraoperative marker.

Approach:

• Developed fluorescently labeled Tsp1a peptide conjugates targeting Na_V1.7 for *in vivo* nerve visualization.
• Characterized Na_V1.7 expression in mouse, primate, and human peripheral nerves, confirming universal presence.
• Evaluated 10 Tsp1a-peptide conjugates for nerve accumulation and signal-to-noise ratio in mice.

Key Points:

• The Tsp1a peptide specifically targets and binds to Na_V1.7 channels on peripheral nerves.
• Tsp1a-IR800 demonstrated high signal-to-noise ratio for nerve delineation in preclinical models.
• Successful demarcation of recurrent laryngeal and vagus nerves in primate thyroidectomies using Tsp1a-IR800.

Conclusions:

• Tsp1a-IR800 effectively enhances nerve contrast during surgical procedures.
• This peptide-based imaging agent has the potential to significantly reduce intraoperative nerve injuries.
• The technology offers a promising advancement for improving surgical safety and standards of care across specialties.