High-frequency ultrasound-guided injection for the generation of a novel orthotopic mouse model of human thyroid carcinoma.

High-frequency ultrasound-guided injection for the generation of a novel orthotopic mouse model of human thyroid carcinoma.

Thyroid. 2016 Feb 4;

Authors: Greco A, Albanese S, Auletta L, Mirabelli P, Zannetti A, D'alterio C, Di Maro G, Orlandella FM, Salvatore G, Soricelli A, Salvatore M

Abstract
BACKGROUND: Thyroid carcinoma is the most common endocrine malignancy and has an increasing incidence. High frequency ultrasound (HFUS) has a spatial resolution of 30 µm, which is a property that has been exploited for thyroid visualization and analysis in mice. The aim of this study was to generate a novel orthotopic mouse model of human follicular thyroid carcinoma (FTC) using an HFUS-guided injection system.
METHODS: Twenty Balb/C nude mice were injected in the right lobe of the thyroid with 2 x 106 FTC-133 cells using the microinjection HFUS-guided system, and 20 mice, used as a control, underwent surgical orthotopic implantation of 2 x 106 FTC-133 cells in the right lobe of the thyroid. All mice underwent HFUS imaging 2 weeks after cell injection; HFUS examinations and tumor volume (TV) measurements were repeated weekly. Micro-CT was performed at different time points to determine whether lung metastasis had occurred. TVs were compared between the two models (surgical versus HFUS-guided) using the Mann-Whitney U test, and the Mantel-Cox log-rank test was applied to evaluate the death hazard. Hematoxylin and eosin (H&E) analysis of formalin-fixed, paraffin-embedded mouse tissue was performed to validate the <i>in vivo</i> imaging results.
RESULTS: Nine of eighteen HFUS-guided injected mice survived up to 40 days after the injection of tumor cells. Mice injected surgically had 100% mortality at day 29. Of 38 mice, 29 (14/18 HFUS, 15/20 surgical) showed metastasis in the salivary glands and lymph nodes, and 13 (10/18 HFUS, 3/20 surgical) also showed metastasis in the lungs, which was confirmed by histological analysis. In the surgical group, there was an evident, frequent (12/20 mice) involvement of the contralateral lobe of the thyroid, whereas this feature was only detected in 1 of 18 mice in the HFUS group. The statistical analysis showed the same pattern of growth in the two groups and a significant hazard in the surgical-group mice (P=0.03).
CONCLUSIONS: In our study, we demonstrated the technical feasibility of an HFUS-guided orthotopic mouse model of FTC. The HFUS-guided orthotopic model is easily reproducible and allows prolonged monitoring of the disease because the animals showed an increased survival rate.

PMID: 26844598 [PubMed - as supplied by publisher]

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