A New Magnetic Resonance Imaging Probe Specifically Targeting Vascular Endothelial Growth Factor Receptor 2:Synthesis, Characterization and Biological Evaluation

Vascular endothelial growth factor (VEGF) is strongly expressed in most tumours and promotes both tumour growth and vascularization. The peptide, VEGF_125-136, consisting of 12 amino acids is encoded by exon 6 of the VEGF gene and inhibits VEGF activity by blocking the binding of VEGF to the VEGFR2 receptor. The aim of the present study was to develop a targeting probe for magnetic resonance imaging (MRI) of tumours by conjugating VEGF_125-136 to gadolinium (III) (Gd(III)) (VGd) through the formation of chelates. The targeting efficiency of VGd to human hepatocellular carcinoma (HCC) cell line, BEL-7402, was subsequently determined both in vitro and in vivo. In the in vitro studies, the MRI results of BEL-7402 cells treated with VGd showed significantly higher T1 signal-to-noise ratio than that of both the competitive group, namely, those treated with VGd and VEGF125-136 and the control group, a scramble peptide conjugated to Gd(III) (SGd). In vivo, when xenografts of BEL-7402 cells were established in mice and then VGd or SGd were injected via tail vein, MRI showed that the tumour signal from VGd initially decreased from 5 to 120 min and then it increased at 120 min post injection. The peak signal was observed at 120 min after injection. In contrast, no distinct peak was observed for SGd. These findings indicate that VGd can target VEGFR2, highly expressed by BEL-7402 cells, enabling targeting MRI with high efficacy to be achieved both in vitro and in vivo.