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BMC Medical Imaging
Published in: BMC Medical Imaging 1/2013

Open Access 01-12-2013 | Technical advance

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

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

Published in: BMC Medical Imaging | Issue 1/2013

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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.
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Metadata
Title
Imaging of thyroid tumor angiogenesis with microbubbles targeted to vascular endothelial growth factor receptor type 2 in mice
Authors
Marcello Mancini
Adelaide Greco
Giuliana Salvatore
Raffaele Liuzzi
Gennaro Di Maro
Emilia Vergara
Gennaro Chiappetta
Rosa Pasquinelli
Arturo Brunetti
Marco Salvatore
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Medical Imaging / Issue 1/2013
Electronic ISSN: 1471-2342
DOI
https://doi.org/10.1186/1471-2342-13-31

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