Ultrasound molecular imaging of heterogeneous tumors to guide therapeutic ultrasound

Propagation through heterogeneous tissues may hamper the ability to correctly focus ultrasound, especially when targeting a tumor for drug delivery applications. To solve this issue, we propose to use ultrasound molecular imaging (USMI) for treatment planning of drug delivery triggered by focused ultrasound. In a model of orthotopic rat prostate tumor having heterogeneous B-mode appearance, we show that tumor extend can be precisely delineated with USMI targeting VEGFR-2 receptors. High intensity ultrasound bursts (Peak negative pressure −15 MPa) are then delivered within this delineated 3D volume to trigger the release of liposomal-encapsulated chemotherapy, by local initiation of inertial cavitation. Real time imaging show that cavitation is indeed restricted to the targeted area. In the animal group receiving both chemotherapy and cavitational ultrasound, a potentiation of the therapeutic effect of the drug is clearly observed. This study demonstrates experimentally that USMI is an effective imaging method to characterize heterogeneous tissues and to guide therapeutic ultrasound.