Perfusion-Guided Monitoring of Tumor Response to Sonoporation and Prediction of Liposomal Doxorubicin Uptake Using Microbubble Contrast Agents

Microbubble ultrasound contrast agents (UCAs) are frequently used for in vivo imaging applications to evaluate changes in tumor perfusion using quantitative contrast enhanced ultrasound (qCEUS) imaging. In addition, volumetric oscillation of these microbubbles in an acoustic field can promote drug extravasation into tumor tissue by permeabilizing cell membranes by a technique known as sonoporation. In this study, we propose that qCEUS imaging can be used to effectively monitor the efficacy of sonoporation in vivo. Importantly, we demonstrate that changes in microbubble perfusion kinetics can function as effective predictors of sonoporation efficiency in vivo. However, the overall degree of tumor perfusion - which is not altered by sonoporation - correlates strongly with drug uptake. Our results suggest that qCEUS can be harnessed to provide real-time feedback detailing vascular changes that occur during sonoporation, and that these biologically driven phenomena can be correlated with nanoparticle uptake in tumors. Successful implementation of this strategy could lead to improved methods of monitoring tumor response to therapy in the clinic, thus furthering strides toward the goal of more personalized therapies.