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Updated: May 26, 2025
A Bright NIR-II Fluorescence Probe for Vascular and Tumor Imaging
Published on: March 17, 2023
Matrix-designed bright near-infrared fluorophores for precision peripheral nerve imaging
Antonio R Montaño1, Anas Masillati1, Dani A Szafran1
1Biomedical Engineering Department, Oregon Health & Science University, Portland, OR 97201, USA.
Abstract:
The FDA's recent approval of pafolacianine, the first molecular targeted contrast agent for fluorescence-guided surgery (FGS), signifies a remarkable milestone in precision medicine. This advance offers new hope for cancer patients by enabling guided removal of cancerous tissues, where completed surgical removal remains a consistent challenge without real-time intraoperative guidance. For optimal surgical outcomes, delicate nerve tissues must be preserved to maintain patient quality of life. Despite advances in the clinical translation pipeline, the development of clinically viable nerve-specific contrast agents for FGS remains a significant challenge. Herein, a medicinal chemistry-based matrix design strategy was applied to effectively generate a synthetic roadmap permitting management of nerve-specificity within the near-infrared (NIR) oxazine fluorophore family. Many of these newly developed fluorophores demonstrated robust nerve-specificity and superior safety profiles, while also offering spectral profiles that are compatible with the clinical surgical FGS infrastructure. Notably, improving observed brightness in vivo enabled exceptional visibility of buried nerve tissue, a priority during surgical procedures. Critically, the lead probe showed a large dosage safety window capable of generating substantial contrast at doses 100x lower than the maximum tolerated dose. Following clinical translation, such NIR nerve-specific fluorophores stand poised to significantly improve outcomes for surgical patients by improving identification and visualization of surface and buried nerve tissues in real time within the surgical arena.
Insights
Researchers developed novel nerve-specific near-infrared (NIR) fluorophores for fluorescence-guided surgery (FGS). These agents enhance surgical precision by improving visualization of critical nerve tissues, leading to better patient outcomes.
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.
