Acoustic characterization and pharmacokinetic analyses of new nanobubble ultrasound contrast agents

Hanping Wu, Nicolas G. Rognin, Tianyi M. Krupka, Luis Solorio, Hiroki Yoshiara, Gilles Guenette, Christopher Sanders, Naohisa Kamiyama, Agata A. Exner

Research output: Contribution to journalArticlepeer-review

106 Scopus citations


In contrast to the clinically used microbubble ultrasound contrast agents, nanoscale bubbles (or nanobubbles) may potentially extravasate into tumors that exhibit more permeable vasculature, facilitating targeted molecular imaging and drug delivery. Our group recently presented a simple strategy using the non-ionic surfactant Pluronic as a size control excipient to produce nanobubbles with a mean diameter of 200nm that exhibited stability and echogenicity on par with microbubbles. The objective of this study was to carry out an in-depth characterization of nanobubble properties as compared with Definity microbubbles, both invitro and invivo. Through use of a tissue-mimicking phantom, invitro experiments measured the echogenicity of the contrast agent solutions and the contrast agent dissolution rate over time. Nanobubbles were found to be more echogenic than Definity microbubbles at three different harmonic frequencies (8, 6.2 and 3.5MHz). Definity microbubbles also dissolved 1.67 times faster than nanobubbles. Pharmacokinetic studies were then performed invivo in a subcutaneous human colorectal adenocarcinoma (LS174T) in mice. The peak enhancement and decay rates of contrast agents after bolus injection in the liver, kidney and tumor were analyzed. No significant differences were observed in peak enhancement between the nanobubble and Definity groups in the three tested regions (tumor, liver and kidney). However, the decay rates of nanobubbles in tumor and kidney were significantly slower than those of Definity in the first 200-s fast initial phase. There were no significant differences in the decay rates in the liver in the initial phase or in three regions of interest in the terminal phase. Our results suggest that the stability and acoustic properties of the new nanobubble contrast agents are superior to those of the clinically used Definity microbubbles. The slower washout of nanobubbles in tumors suggests potential entrapment of the bubbles within the tumor parenchyma.

Original languageEnglish (US)
Pages (from-to)2137-2146
Number of pages10
JournalUltrasound in Medicine and Biology
Issue number11
StatePublished - Nov 2013
Externally publishedYes


  • Cancer
  • Nanobubble
  • Pharmacokinetic study
  • Ultrasound contrast agents

ASJC Scopus subject areas

  • Biophysics
  • Radiological and Ultrasound Technology
  • Acoustics and Ultrasonics


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