AUTHOR=Zhou Yi , Song Zhuqing , Hu Qiao , Ji Xiaojuan , Zheng Hongyu , Wang Xiaoyan , Li Zhenzhou 

TITLE=Evaluation of the Expression of Matrix Metalloproteinase-1 of Laryngeal Squamous Cell Carcinoma by Ultrasound Molecular Imaging

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00655

DOI=10.3389/fphar.2019.00655

ISSN=1663-9812

ABSTRACT=<p><bold>Purpose:</bold> The aims of this study were to evaluate the expression of matrix metalloproteinase-1 (MMP-1) on laryngeal squamous cell carcinoma (LSCC) and improve the early diagnosis rate <italic>via</italic> ultrasound molecular imaging (USMI).</p><p><bold>Methods:</bold> The microsized MMP-1-targeted microbubbles (MB<sub>MMP-1</sub>) and the control MBs (MB<sub>IgG</sub>) based on perfluorocarbon-filled lipid-shelled MBs were constructed and characterized. The <italic>in vitro</italic> binding experiment was performed with human epidermoid laryngeal cancer cells (HEp-2) and tested the binding efficiency of MB<sub>MMP-1</sub> and MB<sub>IgG</sub>. In the <italic>in vivo</italic> study, the LSCC model was established in 10 mice. The MB<sub>MMP-1</sub> and MB<sub>IgG</sub> were randomly injected into tumor-bearing mice <italic>via</italic> the tail vein at Day 7, Day 12, and Day 17 to dynamically evaluate the differential targeted enhancement (dTE) signals <italic>via</italic> USMI. Subsequent immunofluorescence analysis was used for confirmation of MMP-1 expression.</p><p><bold>Result:</bold> The effective adhesion rate of MB<sub>MMP-1</sub> and MB<sub>IgG</sub> to HEp-2 was 298.42 ± 16.57 versus 12.38 ± 3.26 bubbles/per field <italic>in vitro</italic> experiment, which shows a significant difference (<italic>P</italic> &lt; 0.01). The <italic>in vivo</italic> ultrasound molecular imaging (USMI) results demonstrated that dTE signal intensity from MB<sub>MMP-1</sub> was significantly higher than that from the MB<sub>IgG</sub> at Day 7, Day 12, and Day 17 (Day 7, 41.21 ± 15.00 versus 2.25 ± 0.6 a.u., <italic>P</italic> &lt; 0.05; Day 12, 124.64 ± 5.19 versus 11.13 ± 1.13 a.u., <italic>P</italic> &lt; 0. 05; Day 17, 332.01 ± 64.88 versus 42.99 ± 11.9 a.u., <italic>P</italic> &lt; 0.01). Moreover, immunofluorescence analysis further confirmed the expression of MMP-1 in LSCC with a gradual increase with the tumor growth.</p><p><bold>Conclusion:</bold> MB<sub>MMP-1</sub> could be a potential probe that can be used in the early diagnosis of LSCC by USMI.</p>