Gadolinium-Based MRI Contrast Agent for Targeted Imaging of Vascular Endothelial Growth Factor Receptor-2-Expressing Tumors

Abstract

Development of imaging methods that can detect target molecules will be of great significance for non-invasive molecular diagnosis. Vascular endothelial growth factor receptor-2 (VEGFR-2) is a broadly expressed target, and VEGFR-2-specific agents have been used in biological therapy. In this study, amine-reactive coupling was used to label the polypeptide VEGF125–136 with a Gd(DOTA) complex to create a magnetic resonance contrast agent, VEGF125–136-Gd, which binds to VEGFR-2. Using T1-weighted magnetic resonance imaging, we explored the tumor cell-targeting ability of VEGF125–136-Gd and its enhancement of T1-weighted image intensity using human hepatoma (HepG2) cells and found that the signal-to-noise ratio (SNR) increased commensurately with the concentration of VEGF125–136-Gd. At a concentration of 2 mM, the SNR produced by VEGF125–136-Gd was 5.4-fold higher than that produced by a Gd-labelled non-targeting polypeptide (NTPP-Gd) control. We also evaluated the tumor-targeting efficiency of VEGF125–136-Gd in nude mice injected with human hepatoma (HepG2) cells. Preliminary in vivo imaging of VEGFR-2 in tumor tissue revealed a targeting peak 60 min post administration of VEGF125–136-Gd, the intensity of which was 23% higher than the SNR of NTPP-Gd at the same time point. Our findings may help lay the foundation for clinical applications of VEGF125–136-Gd in targeted imaging.