Imaging of thyroid tumor angiogenesis with microbubbles targeted to vascular endothelial growth factor receptor type 2 in mice

Marcello Mancini, Adelaide Greco, Giuliana Salvatore, Raffaele Liuzzi, Gennaro Di Maro, Emilia Vergara, Gennaro Chiappetta, Rosa Pasquinelli, Arturo Brunetti, Marco Salvatore

Research output: Contribution to journalArticle

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 VEGFR-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.

Original languageEnglish
Article number31
JournalBMC Medical Imaging
Volume13
Issue number1
DOIs
Publication statusPublished - Sep 12 2013

Keywords

  • Cancer
  • Contrast agent
  • High resolution ultrasound
  • Thyroid
  • Transgenic

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

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