Ultrasound imaging is a widely used, readily accessible and safe imaging modality. Molecularly-targeted
microbubble- and nanobubble-based
contrast agents used in conjunction with ultrasound imaging expand the utility of this modality by specifically targeting and detecting
biomarkers associated with different pathologies including
cancer. In this study, nanobubbles directed to a
cancer biomarker derived from the
Receptor Protein Tyrosine Phosphatase mu,
PTPmu, were evaluated alongside non-targeted nanobubbles using contrast enhanced ultrasound both in vitro and in vivo in mice. In vitro resonant mass and clinical ultrasound measurements showed gas-core,
lipid-shelled nanobubbles conjugated to either a
PTPmu-directed
peptide or a Scrambled control
peptide were equivalent. Mice with heterotopic human
tumors expressing the
PTPmu-
biomarker were injected with
PTPmu-targeted or control nanobubbles and dynamic contrast-enhanced ultrasound was performed.
Tumor enhancement was more rapid and greater with
PTPmu-targeted nanobubbles compared to the non-targeted control nanobubbles. Peak
tumor enhancement by the
PTPmu-targeted nanobubbles occurred within five minutes of contrast injection and was more than 35% higher than the Scrambled nanobubble signal for the subsequent two minutes. At later time points, the signal in
tumors remained higher with
PTPmu-targeted nanobubbles demonstrating that
PTPmu-targeted nanobubbles recognize
tumors using molecular ultrasound imaging and may be useful for diagnostic and therapeutic purposes.