Molecular Targeted NIR-II Probe for Image-Guided Brain Tumor Surgery

Area of Science:

• Biomedical Optics
• Molecular Imaging
• Neurosurgery

Background:

• Glioblastoma (GBM) delineation is critical for surgical success, requiring advanced imaging techniques.
• Near-infrared-II (NIR-II) fluorescence imaging offers superior tissue penetration and resolution compared to NIR-I.
• Urokinase Plasminogen Activator Receptor (uPAR) is highly expressed in GBM, making it a viable imaging target.

Purpose of the Study:

• To develop and evaluate a targeted NIR-II fluorescent probe for imaging uPAR-expressing GBM.
• To assess the probe's in vivo performance for tumor visualization and surgical guidance.

Main Methods:

• Conjugation of a NIR-II fluorophore (CH1055) with a uPAR-targeting peptide (AE105) to create a targeted probe (CH1055-4Glu-AE105).
• In vivo dynamic imaging in orthotopic GBM-bearing nude mice to assess probe distribution and tumor targeting.
• Fluorescence-guided surgery in living animals to evaluate the probe's utility in real-time resection.

Main Results:

• The synthesized probe CH1055-4Glu-AE105 demonstrated high purity (>98%) and yield (>75%).
• Dynamic imaging revealed successful visualization of orthotopic GBM through the intact skull with a tumor-to-background ratio (TBR) of 2.7 at 96 hours.
• Fluorescence-guided resection of orthotopic GBM was successfully performed in small animals.

Conclusions:

• A small, targeted NIR-II fluorescent probe effectively images and detects GBM.
• Real-time NIR-II fluorescence imaging facilitates targeted tumor resection.
• The developed probe shows significant potential for clinical translation in GBM surgery.