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Use of VEGFR-2 Targeted Ultrasound Contrast Agent for the Early Evaluation of Response to Sorafenib in a Mouse Model of Hepatocellular Carcinoma

Abstract

Purpose

The aim of this study was to assess the early response to sorafenib using ultrasound molecular imaging in a murine model of hepatocellular carcinoma (HCC).

Procedures

A xenograft model of HCC was established. Then, mice were divided in two groups and received treatment (sorafenib) or placebo for 14 days. The treatment group was further divided into non-responders and responders according to the degree of growth. Contrast enhanced ultrasound (CEUS) was performed using VEGFR-2 targeted microbubbles (BR55, Bracco Suisse SA, Geneva, Switzerland). Dedicated software was used to quantify the amount of bound microbubbles in the tumor as a numerical value (differential targeted enhancement (dTE)). Tumors were then excised and western blot analysis performed.

Results

The dTE values decreased from day 0 to day +14 both in the treatment and control groups, but were lower in the former. The non-responder group had higher dTE levels at day 2 compared to responders (p = 0.019).

Conclusion

BR55 appears to be useful in the prediction of response to sorafenib in a xenograft model of HCC.

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Acknowledgments

The authors would express their gratitude to Prof. Francois Tranquart and to Dr. Laurent Mercier, from Bracco, for proving the targeted microbubbles and quantification software without charge. The authors are also grateful to Dr. Laura Porretti and Dr. Federico Colombo, University of Milan, for helpful advice. The study was supported by funds from the Italian Ministry of Health (Project Giovani Ricercatori 038/GR-2009-1606660), without involvement in study design, collection, analysis and interpretation of data, in the writing of the manuscript or in the decision to submit the manuscript for publication.

Conflict of Interest

Bolondi has received speaker fees from Bracco; Piscaglia received honorary lectures fees from Bracco, Siemens and Bayer Healthcare; he acted in advisory boards of GE and Bayer Healthcare; a research contract agreement with Esaote is active in the Department.

Author information

Correspondence to Fabio Piscaglia.

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Baron Toaldo, M., Salvatore, V., Marinelli, S. et al. Use of VEGFR-2 Targeted Ultrasound Contrast Agent for the Early Evaluation of Response to Sorafenib in a Mouse Model of Hepatocellular Carcinoma. Mol Imaging Biol 17, 29–37 (2015). https://doi.org/10.1007/s11307-014-0764-x

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Key words

  • Targeted ultrasonographic contrast media
  • Hepatocellular carcinoma
  • BR55
  • Xenograft model
  • Sorafenib
  • Response to treatment