Accumulation of Phase‐Shift Nanoemulsions to Enhance MR‐Guided Ultrasound‐Mediated Tumor Ablation In Vivo

Abstract

Magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) is being explored as a non-invasive technology to treat solid tumors. However, the clinical use of HIFU for tumor ablation applications is currently limited by the long treatment times required. Phase-shift nanoemulsions (PSNE), consisting of liquid perfluorocarbon droplets that can be vaporized into microbubbles, are being developed to accelerate HIFU-mediated heating. The purpose of this study was to examine accumulation of PSNE in intramuscular rabbit tumors in vivo. MR images were acquired before and after intravenous injection of gadolinium-containing PSNE. MR signal enhancement was observed in rabbit tumors up to six hours after injection, indicating that PSNE accumulated in the tumors. In addition, PSNE vaporization was detected in the tumor with B-mode ultrasound imaging, and MR thermometry measurements indicated that PSNE accelerated the rate of HIFU-mediated heating. These results suggest that PSNE could dramatically improve the efficiency and clinical feasibility of MRgHIFU.

Acoustic Cavitation-Mediated Delivery of Small Interfering Ribonucleic Acids with Phase-Shift Nano-Emulsions

“…Ultrasound can be used to vaporize the perfluorocarbon core and the pressure threshold for vaporization depends upon numerous factors including the boiling point of the perfluorocarbon (Kawabata et al 2005; Sheeran et al 2012), ambient temperature (Fabiilli et al 2009; Zhang and Porter 2010), ultrasound frequency (Kripfgans et al 2000), and size of the droplet (Kripfgans et al 2004; Fabiilli et al 2009). In theory, PSNE vaporization could allow controlled initiation of acoustic cavitation in tissue where bubbles are difficult to form and control (Kopechek et al 2013). PSNE combine the improved biocompatibility, long circulation, and extravasation properties of lipid-based nanoparticles with the beneficial bioeffects of acoustic cavitation, such as sonoporation.…”

“…PSNE combine the improved biocompatibility, long circulation, and extravasation properties of lipid-based nanoparticles with the beneficial bioeffects of acoustic cavitation, such as sonoporation. This unique class of emulsion has been utilized for drug delivery applications (Rapoport et al 2009; Adan et al 2012; Wang et al 2012), contrast-enhanced ultrasound imaging (Sheeran et al 2013b; Williams et al 2013), and bubble-enhanced heating for high intensity focused ultrasound (HIFU) ablation (Kopechek et al 2013; Phillips et al 2013). …”

State-of-the-art materials for ultrasound-triggered drug delivery

“…Due to the acoustic impedance mismatch between PFCE and surrounding tissue, the droplets could be imaged with ultrasound in circulation, allowing for the development of image-guided drug delivery. Similar approaches to dual modality imaging and therapy are being explored with vaporizable nanodrops, such as the development of Gd-coated PFC nanodrops for MR imaging and ultrasound-mediated tissue ablation [117], and image-guided tagging of tissue with fluorescent markers [118]. …”

Phase-transition Perfluorocarbon Nanoparticles for Ultrasound Molecular Imaging and Therapy

“…In the most recent work, the application of enhancing ultrasound/magnetic resonance dual-modality imaging and accelerating the therapeutic efficiency of high intensity focused ultrasound (HIFU) has been observed in rabbit tumors after intravenous injection of gadolinium coated PFC nanoparticles [125]. Similar researches for multiple modality imaging and synergistic HIFU ablation of tumors are being investigated with PFC nanoparticles, such as the development of India ink incorporated phase-transition nanodroplets for photoacoustic/ ultrasound imaging and photoacoustic effect of tumor therapy [126], and a formulation of silica coated PFC nanoemulsion encapsulating camptothecin (CPT) for synergistic effect of chemotherapy and HIFU ablation in rabbit tumors [127].…”