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 200 nm 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 in vitro and in vivo. Through use of a tissue-mimicking phantom, in vitro 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 3.5 MHz).
Definity microbubbles also dissolved 1.67 times faster than nanobubbles. Pharmacokinetic studies were then performed in vivo 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.