title: In vivo tumor targeting and imaging with anti-vascular endothelial growth factor antibody-conjugated dextran-coated iron oxide nanoparticles.
abstract: BACKGROUND
  Active targeting by specific antibodies combined with nanoparticles is a promising technology for cancer imaging and detection by magnetic resonance imaging (MRI). The aim of the present study is to investigate whether the systemic delivery of antivascular endothelial growth factor antibodies conjugating to the surface of functionalized supermagnetic iron oxide nanoparticles (anti-VEGF-NPs) led to target-specific accumulation in the tumor.
  
  
  METHODS
  The VEGF expression in human colon cancer and in Balb/c mice bearing colon cancers was examined by immunohistochemistry. The distribution of these anti-VEGF-NPs particles or NPs particles were evaluated by MRI at days 1, 2, or 9 after the injection into the jugular vein of Balb/c mice bearing colon cancers. Tumor and normal tissues (liver, spleen, lung, and kidney) were collected and were examined by Prussian blue staining to determine the presence and distribution of NPs in the tissue sections.
  
  
  RESULTS
  VEGF is highly expressed in human and mouse colon cancer tissues. MRI showed significant changes in the T*(2) signal and T(2) relaxation in the anti-VEGF-NP- injected-mice, but not in mice injected with NP alone. Examination of paraffin sections of tumor tissues stained for the iron constituent of the NPs with Prussian blue revealed a strong blue reaction in the tumors of anti-VEGF-NP-treated mice, but only a weak reaction in mice injected with NPs. In both groups, at all time points, Prussian blue-stained liver and spleen sections showed only light staining, while stained cells were rarely detected in kidney and lung sections. Transmission electron microscopy showed that many more electron-dense particles were present in endothelial cells, tumor cells, and extracellular matrix in tumor tissues in mice injected with anti-VEGF-NPs than in NP-injected mice.
  
  
  CONCLUSIONS
  These results demonstrated in vivo tumor targeting and efficient accumulation of anti-VEGF-NPs in tumor tissues after systemic delivery in a colon cancer model, showing that anti-VEGF-NPs have potential for use as a molecular-targeted tumor imaging agent in vivo.
authors: Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Wan-Ju
authors: WJ
authors: Hsieh
authors: Chan-Jung
authors: CJ
authors: Liang
authors: Jen-Jie
authors: JJ
authors: Chieh
authors: Shu-Huei
authors: SH
authors: Wang
authors: I-Rue
authors: IR
authors: Lai
authors: Jyh-Horng
authors: JH
authors: Chen
authors: Fu-Hsiung
authors: FH
authors: Chang
authors: Wei-Kung
authors: WK
authors: Tseng
authors: Shieh-Yueh
authors: SY
authors: Yang
authors: Chau-Chung
authors: CC
authors: Wu
authors: Yuh-Lien
authors: YL
authors: Chen
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D003911:Dextrans / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000922:Immunotoxins / Q000008:administration & dosage* / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D013154:Spleen / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D003911:Dextrans; D000922:Immunotoxins; D058185:Magnetite Nanoparticles; D042461:Vascular Endothelial Growth Factor A