Contrast Ultrasound Imaging for Identification of Early Responder Tumor Models to Anti-Angiogenic Therapy

Shashank R. Sirsi, Molly L. Flexman, Fotois Vlachos, Jianzhong Huang, Sonia L. Hernandez, Hyun Keol Kim, Tessa B. Johung, Jeffrey W. Gander, Ari R. Reichstein, Brooke S. Lampl, Antai Wang, Andreas H. Hielscher, Jessica J. Kandel, Darrell J. Yamashiro, Mark A. Borden

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Agents targeting vascular endothelial growth factor (VEGF) have been validated as cancer therapeutics, yet efficacy can differ widely between tumor types and individual patients. In addition, such agents are costly and can have significant toxicities. Rapid noninvasive determination of response could provide significant benefits. We tested if response to the anti-VEGF antibody bevacizumab (BV) could be detected using contrast-enhanced ultrasound imaging (CEUS). We used two xenograft model systems with previously well-characterized responses to VEGF inhibition, a responder (SK-NEP-1) and a non-responder (NGP), and examined perfusion-related parameters. CEUS demonstrated that BV treatment arrested the increase in blood volume in the SK-NEP-1 tumor group only. Molecular imaging of αVβ3 with targeted microbubbles was a more sensitive prognostic indicator of BV efficacy. CEUS using RGD-labeled microbubbles showed a robust decrease in αVβ3 vasculature following BV treatment in SK-NEP-1 tumors. Paralleling these findings, lectin perfusion assays detected a disproportionate pruning of smaller, branch vessels. Therefore, we conclude that the response to BV can be identified soon after initiation of treatment, often within 3 days, by use of CEUS molecular imaging techniques. The use of a noninvasive ultrasound approach may allow for earlier and more effective determination of efficacy of antiangiogenic therapy.

Original languageEnglish (US)
Pages (from-to)1019-1029
Number of pages11
JournalUltrasound in Medicine and Biology
Volume38
Issue number6
DOIs
StatePublished - Jun 1 2012

Keywords

  • Bevacizumab
  • Blood volume
  • Ewings family tumor
  • Microbubble
  • Molecular imaging
  • Neuroblastoma
  • VEGF blockade

ASJC Scopus subject areas

  • Biophysics
  • Radiological and Ultrasound Technology
  • Acoustics and Ultrasonics

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  • Cite this

    Sirsi, S. R., Flexman, M. L., Vlachos, F., Huang, J., Hernandez, S. L., Kim, H. K., Johung, T. B., Gander, J. W., Reichstein, A. R., Lampl, B. S., Wang, A., Hielscher, A. H., Kandel, J. J., Yamashiro, D. J., & Borden, M. A. (2012). Contrast Ultrasound Imaging for Identification of Early Responder Tumor Models to Anti-Angiogenic Therapy. Ultrasound in Medicine and Biology, 38(6), 1019-1029. https://doi.org/10.1016/j.ultrasmedbio.2012.01.014