Molecular ultrasound imaging using a targeted contrast agent for assessing early tumor response to antiangiogenic therapy

Anna G. Sorace, Reshu Saini, Marshall Mahoney, Kenneth Hoyt

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Objectives-Contrast-enhanced ultrasound (US) and targeted microbubbles have been shown to be advantageous for angiogenesis evaluation and disease staging in cancer. This study explored molecular US imaging of a multitargeted microbubble for assessing the early tumor response to antiangiogenic therapy. Methods-Targetreceptor expression of2LMPbreast cancer cellswasquantified by flow cytometric analysisandcharacterization established with antibodies againstmouseαVβ3- integrin, P-selectin, and vascular endothelial growth factor receptor 2. Tumor-bearing mice (n = 15 per group) underwent contrast-enhanced US imaging of multitargeted microbubbles. Microbubble accumulation was calculated by destruction-replenishment techniquesandtime-intensity curve analysis. On day 0, mice underwent baseline imaging. Next, therapy group mice were injected with a 0.2-mg dose of bevacizumab, and controls received matched saline injections. Imaging was repeated on days 1 and 3. After imaging was completed on day 3, the mice were euthanized and tumors excised. Histologic analysis of microvessel density and intratumoral necrosis was completed on tumor sections. Results-Onday 3 after bevacizumab dosing, a 71.8% change in tumor vasculaturewas shown between the therapy and control groups (P = .01). The therapy group had a 15.4% decrease in tumor vascularity, whereas the control group had a 56.4% increase. Conclusions- MolecularUSimaging of angiogenic markers can detect the early tumor response to drug therapy.

Original languageEnglish (US)
Pages (from-to)1543-1550
Number of pages8
JournalJournal of Ultrasound in Medicine
Volume31
Issue number10
DOIs
StatePublished - Oct 1 2012

Keywords

  • Angiogenesis
  • Antiangiogenic therapy
  • Contrast-enhanced ultrasound
  • Microbubbles
  • Targeted contrast agent

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

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