Clinically Translatable Formulation Strategies for Systemic Administration of Nerve-Specific Probes

Nerves are extremely difficult to identify and are often accidently damaged during surgery, leaving patients with lasting pain and numbness. Herein, a novel near-infrared (NIR) nerve-specific fluorophore, LGW01-08, is utilized for enhanced nerve identification using fluorescence guided surgery (FGS), formulated using clinical translatable strategies. Formulated LGW01-08 is examined for toxicology, pharmacokinetics, and pharmacodynamics parameters in preparation for future clinical translation. Optimal LGW01-08 imaging doses are identified in each formulation resulting in a 10x difference between the toxicity and imaging dose window. Laparoscopic swine surgery completed using the da Vinci surgical robot (Intuitive Surgical) demonstrates the efficacy of formulated LGW01-08 for enhanced nerve identification. NIR fluorescence imaging enables clear identification of nerves buried beneath approximate to 3 mm of tissue that are unidentifiable by white light imaging. These studies provide a strong basis for future clinical translation of NIR nerve-specific fluorophores for utility during FGS to improve patient outcomes.