Near‐Infrared II Fluorescence Imaging Highlights Tumor Angiogenesis in Hepatocellular Carcinoma with a VEGFR‐Targeted Probe

Abstract Hepatocellular carcinoma (HCC) is typically characterized by rich vascularity, with angiogenesis playing a crucial role in its growth and invasion. Molecular imaging of specific receptors in blood vessels is crucial in HCC diagnosis. In particular, in vivo imaging utilizing the second near‐infrared (NIR‐II) window offers improved tissue penetration, reduced light scattering, and lower autofluorescence. Despite the great potential of the NIR‐II window, developing safe and effective probes to provide better imaging performance for HCC is urgently needed. In this study, NIR‐II imaging integrated with a vascular endothelial growth factor receptor (VEGFR)‐targeted probe generated by combining a VEGFR‐targeted peptide with indocyanine green (ICG) is used to characterize HCC‐related angiogenesis at a resolution of 56.0 µm. For the first time, liver metabolic curves and parameters of liver function reserve (LFR) are obtained by fitting NIR‐II fluorescence signals with high spatiotemporal resolution, showing significant differences between HCC mice and controls. Moreover, unlike ICG, the targeting probe has a targeted effect on blood vessels in vivo. The tumor‐to‐normal (T/N) ratio in NIR‐II imaging reaches up to 3.30 after post‐injection of the targeting probe. The results indicate that the VEGFR‐targeted probe is a powerful tool for NIR‐II fluorescence imaging to enhance early diagnosis of HCC.