Matrix-designed bright near-infrared fluorophores for precision peripheral nerve imaging

Area of Science:

• Medicinal Chemistry
• Surgical Oncology
• Biomedical Imaging

Background:

• Fluorescence-guided surgery (FGS) utilizes molecular targeted contrast agents for real-time intraoperative guidance.
• Pafolacianine, the first FDA-approved agent, marks progress in precision medicine for cancer surgery.
• Preserving delicate nerve tissues during surgery is crucial for patient quality of life, yet challenging without adequate visualization.

Purpose of the Study:

• To develop clinically viable, nerve-specific contrast agents for enhanced fluorescence-guided surgery (FGS).
• To create novel near-infrared (NIR) oxazine fluorophores with improved nerve visualization capabilities.
• To ensure developed agents possess favorable safety profiles and spectral compatibility with existing FGS infrastructure.

Main Methods:

• Employed a medicinal chemistry-based matrix design strategy to synthesize a novel series of NIR oxazine fluorophores.
• Evaluated fluorophores for nerve-specificity, safety profiles, spectral characteristics, and in vivo brightness.
• Assessed the lead probe's dosage safety window and contrast generation capabilities.

Main Results:

• Newly developed fluorophores demonstrated robust nerve-specificity and superior safety profiles.
• Optimized spectral profiles are compatible with clinical surgical FGS infrastructure.
• Improved in vivo brightness enabled exceptional visibility of both surface and buried nerve tissues; lead probe showed a large dosage safety window.

Conclusions:

• Novel NIR nerve-specific fluorophores offer a significant advancement for FGS.
• These agents are poised to improve surgical outcomes by enhancing real-time identification and visualization of critical nerve tissues.
• The developed technology has the potential to minimize nerve damage and improve patient quality of life during oncologic surgeries.