Imaging of thyroid tumor angiogenesis with microbubbles targeted to vascular endothelial growth factor receptor type 2 in mice
1 Institute of Biostructure and Bioimaging, Italian National Research Council (CNR), Naples, Italy
2 SDN Foundation IRCCS, Naples, Italy
3 Dipartimento di Scienze Biomediche Avanzate, Università degli Studi di Napoli “Federico II”, Naples, 80131, Italy
4 Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Università degli Studi di Napoli “Parthenope”, Naples, Italy
5 CEINGE-Biotecnologie Avanzate s.c.a.\r.l., Naples, Italy
6 Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università degli Studi di Napoli “Federico II”, Naples, 80131, Italy
7 Functional Genomic Unit, Istituto Nazionale Tumori G. Pascale, Naples, Italy
BMC Medical Imaging 2013, 13:31 doi:10.1186/1471-2342-13-31Published: 12 September 2013
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).
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.
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).
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.