Despite
recent advancements in colorectal cancer (CRC) treatment,
the prognosis remains unfavorable primarily due to high recurrence
and liver metastasis rates. Fluorescence molecular imaging technologies,
combined with specific probes, have gained prominence in facilitating
real-time tumor resection guided by fluorescence. Hepatocyte growth
factor (HGF) is overexpressed in CRC, but the advancement of HGF fluorescent
probes has been impeded by the absence of effective HGF-targeting
small-molecular ligands. Herein, we present the targeted capabilities
of the novel V-1-GGGK-MPA probe labeled with a near-infrared fluorescent
dye, which targets HGF in CRC. The V-1-GGGK peptide exhibits high
specificity and selectivity for HGF-positive in vitro tumor cells and in vivo tumors. Biodistribution
analysis of V-1-GGGK-MPA revealed tumor-specific accumulation with
low background uptake, yielding signal-to-noise ratio (SNR) values
of tumor-to-colorectal >6 in multiple subcutaneous CRC models 12
h
postinjection. Quantitative analysis confirmed the probe’s
high uptake in SW480 and HT29 orthotopic and liver metastatic models,
with SNR values of tumor-to-colorectal and -liver being 5.6 ±
0.4, 4.6 ± 0.5, and 2.1 ± 0.3, 2.0 ± 0.5, respectively,
enabling precise tumor visualization for surgical navigation. Pathological
analysis demonstrated the excellent tumor boundaries discrimination
capacity of the V-1-GGGK-MPA probe at the molecular level. With its
rapid tumor targeting, sustained tumor retention, and precise tumor
boundary delineation, V-1-GGGK-MPA merges as a promising HGF imaging
agent, enriching the toolbox of intraoperative navigational fluorescent
probes for CRC.