Effect of microbubble and acoustic radiation force parameters on αvβ3–microbubble targeting

Abstract

Ultrasound molecular imaging (USMI) employs targeted microbubbles (MBs) decorated with specific ligands to enhance the local visualization of vascular structures. It has been demonstrated that cyclo Arg-Gly-Asp (cRGD) targeted MBs in combination with acoustic radiation force (ARF) can bind to αvβ3 integrins providing enhanced images of the tumor vasculature. Therefore, the goal of this work was to study and elucidate the role of ARF and MB parameters on the targeting of cRGD-MBs using an in vitro αvβ3-coated microvessel phantom. Labeled polydisperse and 2-μm size- isolated MBs decorated with cRGD with buried-ligand architecture (BLA) were pumped at 1 ml/h in an αvβ3-coated microvessel (D = 200 μm) and pushed using ARF. At higher monodisperse MB concentrations, the specific attachment follows a linear behavior independent of the frequency applied. However, at lower MB concentrations, the attachment becomes linearly dependent on the frequency. Finally, attachment of monodisperse population of RGD-MBs increased 8- and 3- fold than polydisperse MBs. In conclusion, we elucidated that the use of a monodisperse population of MBs improves the molecular specificity for αvβ3 integrins.