Molecular imaging of tumor angiogenesis using RGD-labeled iron oxide nanoparticles

作者:Wu XinYing; Zhang JingFeng; Lin BingYing; Zhang MinMing*
来源:Chinese Science Bulletin, 2010, 55(24): 2662-2670.
DOI:10.1007/s11434-010-4004-8

摘要

Integrin is often significantly upregulated in activated endothelial cells during tumor angiogenesis. The arginine-glycine-aspartic acid (RGD) peptide sequence is a specific recognition motif to alpha(v)beta(3) 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 T-2*-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 visualize alpha(v)beta(3) integrin in activated tumor endothelial cells and its potential for detecting and monitoring tumor vasculature change after therapy.