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

BMC Medical Imaging

Marco Salvatore²  Arturo Brunetti⁴  Rosa Pasquinelli¹  Gennaro Chiappetta¹  Emilia Vergara²  Gennaro Di Maro⁷  Raffaele Liuzzi⁵  Giuliana Salvatore³  Adelaide Greco⁴  Marcello Mancini⁶ 

[1] Functional Genomic Unit, Istituto Nazionale Tumori G. Pascale, Naples, Italy;Dipartimento di Scienze Biomediche Avanzate, Università degli Studi di Napoli “Federico II”, Naples, 80131, Italy;Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Università degli Studi di Napoli “Parthenope”, Naples, Italy;CEINGE-Biotecnologie Avanzate s.c.a.\r.l., Naples, Italy;Institute of Biostructure and Bioimaging, Italian National Research Council (CNR), Naples, Italy;SDN Foundation IRCCS, Naples, Italy;Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università degli Studi di Napoli “Federico II”, Naples, 80131, Italy

关键词: Contrast agent;    Cancer;    High resolution ultrasound;    Transgenic;    Thyroid;   

Others  :  1090592
DOI  :  10.1186/1471-2342-13-31

 received in 2013-04-08, accepted in 2013-09-06,  发布年份 2013

【 摘 要 】

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 (UCA_VEGFR-2) and isotype control antibody (UCA_IgG) 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 (VI_D) caused by backscatter of the retained UCA_VEGFR-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 VI_D were observed in the group of mice carrying benign nodules compared to mice with normal thyroids. Moreover in thyroid tumors VI_D of retained VEGFR-2-targeted UCA was significantly higher than that of control UCA_IgG (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 UCA_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.

【 授权许可】

   
2013 Mancini et al.; licensee BioMed Central Ltd.

【 图 表 】

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