title: Imaging of thyroid tumor angiogenesis with microbubbles targeted to vascular endothelial growth factor receptor type 2 in mice.
abstract: BACKGROUND
  To evaluate whether Contrast Enhanced Ultrasund (CEUS) with microbubbles (MBs) targeted to VEGFR-2 is able to characterize in vivo the VEGFR-2 expression in the tumor vasculature of a mouse model of thyroid cancer (Tg-TRK-T1).
  
  
  METHODS
  Animal protocol was approved by Institutional committee on Laboratory Animal Care. Contrast-enhanced ultrasound imaging with MBs targeted with an anti-VEGFR-2 monoclonal antibody (UCAVEGFR-2) and isotype control antibody (UCAIgG) was performed in 7 mice with thyroid carcinoma, 5 mice with hyperplasia or benign thyroid nodules and 4 mice with normal thyroid. After ultrasonography, the tumor samples were harvested for histological examination and VEGFR-2 expression was tested by immunohistochemistry. Data were reported as median and range. Paired non parametric Wilcoxon's test and ANOVA of Kruskal-Wallis were used. The correlation between the contrast signal and the VEGFR-2 expression was assessed by the Spearman coefficient.
  
  
  RESULTS
  The Video intensity difference (VID) caused by backscatter of the retained UCAVEGFR-2 was significantly higher in mice harboring thyroid tumors compared to mice with normal thyroids (P < 0.01) and to mice harboring benign nodules (P < 0.01). No statistically significant differences of VID were observed in the group of mice carrying benign nodules compared to mice with normal thyroids. Moreover in thyroid tumors VID of retained VEGFR-2-targeted UCA was significantly higher than that of control UCAIgG (P <0.05). Results of immunohistochemical analysis confirmed VEGFR-2 overexpression. The magnitude of the molecular ultrasonographic signal from a VEGFR-2-targeted UCA retained by tissue correlates with VEGFR-2 expression determined by immunohistochemistry (rho 0.793, P=0.0003).
  
  
  CONCLUSIONS
  We demonstrated that CEUS with UCAVEGFR-2 might be used for in vivo non invasive detection and quantification of VEGFR-2 expression in thyroid cancer in mice, and to differentiate benign from malignant thyroid nodules.
authors.affiliation: Institute of Biostructure and Bioimaging, Italian National Research Council (CNR), Naples, Italy. marcello.mancini58@gmail.com.
authors.forename: Marcello
authors.initials: M
authors.lastname: Mancini
authors.forename: Adelaide
authors.initials: A
authors.lastname: Greco
authors.forename: Giuliana
authors.initials: G
authors.lastname: Salvatore
authors.forename: Raffaele
authors.initials: R
authors.lastname: Liuzzi
authors.forename: Gennaro
authors.initials: G
authors.lastname: Di Maro
authors.forename: Emilia
authors.initials: E
authors.lastname: Vergara
authors.forename: Gennaro
authors.initials: G
authors.lastname: Chiappetta
authors.forename: Rosa
authors.initials: R
authors.lastname: Pasquinelli
authors.forename: Arturo
authors.initials: A
authors.lastname: Brunetti
authors.forename: Marco
authors.initials: M
authors.lastname: Salvatore
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D003287:Contrast Media / Q000493:pharmacokinetics*; D051379:Mice; D008822:Mice, Transgenic; D057054:Molecular Imaging / Q000379:methods; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D014463:Ultrasonography / Q000379:methods*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; D040301:Vascular Endothelial Growth Factor Receptor-2
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