Molecular imaging of tumor-associated biomarkers is a key strategy to advance precision cancer diagnosis and improve intraoperative decision-making. The vascular endothelial growth factor receptor 2 (VEGFR2) is a principal regulator of tumor angiogenesis and therefore represents a clinically relevant target for imaging agents intended to identify vascularized tumor tissue. Although indocyanine green (ICG) is widely used clinically for near-infrared imaging, its short circulation half-life and lack of active targeting limit its effectiveness for tumor-specific intraoperative navigation.
The study reported here addresses these limitations by developing a VEGFR2-targeted fluorescent probe that combines active targeting, extended circulation, and established fluorescent chemistry to improve tumor contrast and enable surgical guidance.
The authors designed a novel VEGFR2-targeting peptide named VTP. VTP is a concatenation of three functional modules: the K237 targeting peptide sequence (HTMYYHHYQHHL), a flexible tripeptide linker (Ser-Ser-Ser, SSS), and an albumin-binding peptide (ABP, DICLPRWGCLWED). The ABP module was included to prolong blood residence time and enhance tumor accumulation via albumin binding.
To generate a fluorescent imaging agent, VTP was conjugated to ICG, producing the targeted probe referred to as ICG-VTP. This construct leverages clinically validated ICG fluorescence while adding active VEGFR2 targeting and albumin-mediated half-life extension.
Surface plasmon resonance (SPR) analysis was used to quantify the interaction between VTP and VEGFR2. The reported dissociation constant (KD) was 15.4 nM, indicating high binding affinity of the peptide for the receptor. The abstract does not report additional in vitro functional assays or cellular binding data in detail; those specifics were not reported in the source abstract.
The probe was evaluated in multiple tumor xenograft models chosen to represent different levels of VEGFR2 expression: a high-expressing ovarian cancer model (SKOV3), a moderate-expressing colorectal cancer model (HCT116), and a low-expressing non-small cell lung cancer model (A549). Owing to the ABP modification, ICG-VTP exhibited a longer blood half-life compared with unconjugated ICG, and probe accumulation in tumors showed a positive correlation with their VEGFR2 expression levels across these models.
The abstract indicates that imaging assessments were performed up to 10 hours post-injection, a timepoint used to report tumor-to-background contrast metrics.
Tumor-to-background ratios (TBRs) measured at 10 hours after administration of ICG-VTP varied with tumor VEGFR2 expression. Reported TBRs were 2.95 for the high VEGFR2-expressing SKOV3 tumors, 2.05 for the moderate HCT116 tumors, and 1.42 for the low A549 tumors. These values support receptor-specific accumulation and improved imaging contrast in VEGFR2-positive tumors compared with lower-expressing lesions.
The abstract highlights that the probe achieved superior imaging contrast for VEGFR2-positive tumors, consistent with the intended design of targeted NIR imaging agents.
Using ICG-VTP for intraoperative fluorescence guidance, the authors report successful fluorescence navigation and precise tumor resection in the studied models. The probe’s tumor contrast at the evaluated timepoint enabled surgical localization and removal of tumor tissue under fluorescence guidance. The abstract does not provide granular operative metrics (for example, margin status or residual disease quantification); such details were not reported in the source abstract.
Safety assessments described in the abstract indicated no significant toxicity at the cellular or tissue levels following use of the probe. The source states that no notable toxicity was observed, but specific toxicology protocols, dose ranges, or histopathologic data are not detailed in the abstract.
The study presents ICG-VTP as a VEGFR2-targeted NIR-II fluorescent probe that combines a high-affinity targeting peptide (KD = 15.4 nM), albumin-binding-mediated half-life extension, and clinically relevant ICG fluorescence. In multiple xenograft models with varying VEGFR2 expression, the probe accumulated in tumors in proportion to receptor expression and produced measurable tumor-to-background ratios at 10 hours post-injection (2.95 for SKOV3, 2.05 for HCT116, 1.42 for A549). The probe enabled intraoperative fluorescence navigation and precise tumor resection in these preclinical models, and reported safety assessments found no significant cellular or tissue toxicity.
Taken together, these results support further preclinical development of ICG-VTP and suggest potential for clinical translation to improve imaging contrast and surgical navigation in VEGFR2-positive tumors. The abstract, however, does not provide full experimental details, including expanded safety studies, pharmacokinetic parameters, or clinical feasibility data, which would be needed to advance toward human studies.