title: Noninvasive monitoring of early antiangiogenic therapy response in human nasopharyngeal carcinoma xenograft model using MRI with RGD-conjugated ultrasmall superparamagnetic iron oxide nanoparticles.
abstract: OBJECTIVE
  Arginine-glycine-aspartic acid (RGD)-based nanoprobes allow specific imaging of integrin αvβ3, a protein overexpressed during angiogenesis. Therefore, this study applied a novel RGD-coupled, polyacrylic acid (PAA)-coated ultrasmall superparamagnetic iron oxide (USPIO) (referred to as RGD-PAA-USPIO) in order to detect tumor angiogenesis and assess the early response to antiangiogenic treatment in human nasopharyngeal carcinoma (NPC) xenograft model by magnetic resonance imaging (MRI).
  
  
  METHODS
  The binding specificity of RGD-PAA-USPIO with human umbilical vein endothelial cells (HUVECs) was confirmed by Prussian blue staining and transmission electron microscopy in vitro. The tumor targeting of RGD-PAA-USPIO was evaluated in the NPC xenograft model. Later, mice bearing NPC underwent MRI at baseline and after 4 and 14 days of consecutive treatment with Endostar or phosphate-buffered saline (n=10 per group).
  
  
  RESULTS
  The specific uptake of the RGD-PAA-USPIO nanoparticles was mainly dependent on the interaction between RGD and integrin αvβ3 of HUVECs. The tumor targeting of RGD-PAA-USPIO was observed in the NPC xenograft model. Moreover, the T2 relaxation time of mice in the Endostar-treated group decreased significantly compared with those in the control group both on days 4 and 14, consistent with the immunofluorescence results of CD31 and CD61 (P<0.05).
  
  
  CONCLUSIONS
  This study demonstrated that the magnetic resonance molecular nanoprobes, RGD-PAA-USPIOs, allow noninvasive in vivo imaging of tumor angiogenesis and assessment of the early response to antiangiogenic treatment in NPC xenograft model, favoring its potential clinical translation.
authors.affiliation: Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine.
authors.forename: Caiyuan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine.
authors.forename: Ran
authors.initials: R
authors.lastname: Luo
authors.affiliation: Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine.
authors.forename: Zhongyang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: MR Advanced Application and Research Center, GE Healthcare China, Shanghai, People's Republic of China.
authors.forename: Tianyong
authors.initials: T
authors.lastname: Xu
authors.affiliation: MR Advanced Application and Research Center, GE Healthcare China, Shanghai, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine.
authors.forename: Dengbin
authors.initials: D
authors.lastname: Wang
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D002277:Carcinoma; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D009389:Neovascularization, Pathologic; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D010316:Particle Size; D016896:Treatment Outcome
chemical_list: D000180:Acrylic Resins; D039302:Integrin alphaVbeta3; D058185:Magnetite Nanoparticles; D009842:Oligopeptides; C006903:carbopol 940; C047981:arginyl-glycyl-aspartic acid
keywords: Endostar; antiangiogenic therapy; integrin αvβ3; magnetic resonance imaging; nasopharyngeal carcinoma; ultrasmall superparamagnetic iron oxide