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Integrin is often significantly up-regulated in activated endothelial cells during tumor angiogenesis.The arginine-glycine-aspartic acid(RGD)peptide sequence is a specific recognition motif toανβ3 integrin.In this study,a RGD labeled,Poly lactic acid(PLA) coated ultrasmall paramagnetic iron oxide(USPIO)(referred to as RGD-PLA-USPIO)were developed and the ability to detect tumor angiogenesis was investigated in vitro and in vivo.Increased uptake of RGD-PLA-USPIO by human umbilical vein endothelial cells(HUVECs)was detected by Prussian blue stain and transmission electronic microscopy(TEM).Pronounced signal decrease in T2*-weighted magnetic resonance image(MRI)and heterogeneous arrangement of neovasculature of tumor tissue were clearly identified in Vx-2 tumor model.The MR signal of contralateral muscle only could be seen a slight background change after either RGD-PLA-USPIO or PLA-USPIO injection.These studies demonstrate the efficiency of RGD-PLA-USPIO to visualizeανβ3 integrin in activated tumor endothelial cells and its potential for detecting and monitoring tumor vasculature change after therapy.
Integrin is often significantly up-regulated in activated endothelial cells during tumor angiogenesis. The arginine-glycine-aspartic acid (RGD) peptide sequence is a specific recognition motif to ανβ3 integrin. In this study, a RGD labeled, Polylactic acid ultrasmall paramagnetic iron oxide (USPIO) (referred to as RGD-PLA-USPIO) were developed and the ability to detect tumor angiogenesis was investigated in vitro and in vivo. Increased uptake of RGD-PLA-USPIO by human umbilical vein endothelial cells ) was detected by Prussian blue stain and transmission electronic microscopy (TEM). Pronounced signal decrease in T2 * -weighted magnetic resonance image (MRI) and heterogeneous arrangement of neovasculature of tumor tissue were clearly identified in Vx-2 tumor model. MR signal of contralateral muscle only could have seen a slight background change after either RGD-PLA-USPIO or PLA-USPIO injection. these studies demonstrate the efficiency of RGD-PLA-USPIO to visualize ανβ3 integrin i n activated tumor endothelial cells and its potential for detecting and monitoring tumor vasculature change after therapy.