Preclinical Evaluation of Rationally Designed Peptide-NIRF Probe for c-Met Positive Liver Cancer Imaging-Guided...

Area of Science:

• Oncology
• Biomedical Engineering
• Molecular Imaging

Background:

• Hepatocellular carcinoma (HCC) recurrence is a major challenge due to occult metastases.
• The c-Met receptor is overexpressed in HCC and serves as a potential biomarker.
• Accurate intraoperative guidance is crucial for complete tumor resection.

Purpose of the Study:

• To develop and evaluate a near-infrared fluorescence (NIRF) probe for c-Met positive HCC detection and surgical navigation.
• To assess the probe's specificity, affinity, and performance in preclinical models.
• To explore the probe's potential for improving HCC diagnosis and surgical outcomes.

Main Methods:

• Conjugation of a high-affinity peptide ligand (GM-7) with a fluorescent dye (MPA) to create the GM-7-MPA probe.
• In vitro assessment of probe specificity and binding affinity for c-Met positive HCC cells.
• In vivo evaluation in various HCC mouse models (subcutaneous xenograft, orthotopic liver cancer, pulmonary metastasis).
• Assessment of probe performance in fluorescence-guided surgical navigation.

Main Results:

• GM-7-MPA exhibited high specificity and strong binding affinity for c-Met positive HCC cells.
• The probe successfully visualized tumor lesions in vivo with a high tumor-to-background ratio (TBR).
• GM-7-MPA accurately delineated tumor margins and identified residual microfoci during surgical navigation studies.
• Complete tumor resection was facilitated by the probe in preclinical models.

Conclusions:

• GM-7-MPA is a promising NIRF probe for the diagnosis and surgical navigation of c-Met positive HCC.
• The probe demonstrates significant translational potential for clinical application in HCC management.
• GM-7-MPA can enhance surgical precision and potentially improve patient survival rates.