Specific targeting of the vasculature of gastric cancer by a new tumor-homing peptide CGNSNPKSC.

Discovery of tumor vascular specific molecules to improve the targeting ability of cytotoxic agents plays an important role in antiangiogenesis. We had found a peptide GX1 (CGNSNPKSC) binding to vasculature endothelial cells of human gastric cancer by phage display technology and its specificity to vasculature had been thoroughly confirmed in vitro. To further evaluate the applicability of GX1 in antiangiogenesis therapy of gastric cancer, immunohistochemical analysis and ECT imaging in nude mice were performed. Immunohistochemical analysis showed that GX1 phage produced positive staining on 51/65 (78%) cases of the vasculature of gastric cancer. Simultaneously GX1 peptide was labeled with (99)Tc(m)O(4)(-), which obtained with high labeling efficiency. (99)Tc(m)-GX1 could specifically bind to Co-HUVEC and HUVEC with a binding constant of 3062 pM and 3831 pM respectively. ECT imaging indicated that GX1 could efficiently target to xenographic tissue in mice model with a high tumor/heart radio than that of control peptide. Biodistribution showed that tumor uptake was 0.74+/-0.02% ID/g at 24 h, 11 times than that of muscle. Immunofluorescence showed GX1 peptide could bind to xenograft vasculature in vivo. The results confirmed the targeting specificity of GX1 in gastric cancer-associated angiogenesis. It would be promising to further develop GX1 peptide-based assay for tumor angiogenesis imaging to improve diagnosis and internal radiotherapy.