Simplified Preparation of αvβ3 Integrin-Targeted Microbubbles Based on a Clinically Available Ultrasound Contrast Agent: Validation in a Tumor-Bearing Mouse Model

Kentaro Otani, Hirohito Nishimura, Atsunori Kamiya, Mariko Harada-Shiba

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The usefulness of ultrasound molecular imaging with αvβ3 integrin-targeted microbubbles for detecting tumor angiogenesis has been demonstrated. Recently, we developed αvβ3 integrin-targeted microbubbles by modifying clinically available microbubbles (Sonazoid, Daiichi-Sankyo Pharmaceuticals, Tokyo, Japan) with a secreted glycoprotein (lactadherin). The aims of our present study were to simplify the preparation of lactadherin-bearing Sonazoid and to examine the diagnostic utility of lactadherin-bearing Sonazoid for αvβ3 integrin-expressing tumor vessels by using SK-OV-3-tumor–bearing mice. By incubating 1.2 × 107 Sonazoid microbubbles with 1.0 µg lactadherin, the complicated washing and centrifugation steps during the microbubble preparation could be omitted with no significant reduction in labeling ratio of lactadherin-bearing Sonazoid. In addition, the number of Sonazoid microbubbles accumulated in the SK-OV-3 tumor was significantly increased by modifying Sonazoid with lactadherin. Our data suggest that the lactadherin-bearing Sonazoid is an easily prepared and potentially clinically translatable targeted microbubble for αvβ3 integrin-expressing vessels.

Original languageEnglish
Pages (from-to)1063-1073
Number of pages11
JournalUltrasound in Medicine and Biology
Volume44
Issue number5
DOIs
Publication statusPublished - May 2018
Externally publishedYes

Keywords

  • Lactadherin
  • Microbubbles
  • Sonazoid
  • Tumor angiogenesis
  • Ultrasound molecular imaging

ASJC Scopus subject areas

  • Biophysics
  • Radiological and Ultrasound Technology
  • Acoustics and Ultrasonics

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