Extended Lifetime <italic>In Vivo</italic> Pulse Stimulated Ultrasound Imaging

Abstract

An on-demand long-lived ultrasound contrast agent that can be activated with single pulse stimulated imaging (SPSI) has been developed using hard shell liquid perfluoropentane filled silica 500-nm nanoparticles for tumor ultrasound imaging. SPSI was tested on LnCAP prostate tumor models in mice; tumor localization was observed after intravenous (IV) injection of the contrast agent. Consistent with enhanced permeability and retention, the silica nanoparticles displayed an extended imaging lifetime of 3.3±1 days (mean±standard deviation). With added tumor specific folate functionalization, the useful lifetime was extended to 12 ± 2 days; in contrast to ligand-based tumor targeting, the effect of the ligands in this application is enhanced nanoparticle retention by the tumor. This paper demonstrates for the first time that IV injected functionalized silica contrast agents can be imaged with an in vivo lifetime ~500 times longer than current microbubble-based contrast agents. Such functionalized long-lived contrast agents may lead to new applications in tumor monitoring and therapy.

MRI‐guided transurethral insonation of silica‐shell phase‐shift emulsions in the prostate with an advanced navigation platform

“…Difficulties in visualizing and confirming injection sites also underscore the need for an IV injection and targeted sUPEs that accumulate preferentially at tumor locations. A study involving intravenous injection of similar 500‐nm particles has demonstrated uptake and retention in LnCAP prostate tumors implanted in the flanks of mice for an average of 3.3 days . When tumor‐specific folate functionalization was added, the particles’ in vivo lifetime was extended to 12 days …”

“…In addition to being more frequent in the experimental treatment arms, the presence of thermal fixation correlated significantly with larger lesions and higher therapeutic temperatures, indicating that the presence of sUPEs could enhance heat deposition with TULSA. Intravenous injection of functionalized or ligand‐targeted sUPEs may improve the specificity of sUPEs for prostate cancer tissue, enhancing TULSA ablation of target areas. Increased absorption by sUPEs would also shield distal structures, allowing extension of treatment margins around the target.…”

“…A study involving intravenous injection of similar 500-nm particles has demonstrated uptake and retention in LnCAP prostate tumors implanted in the flanks of mice for an average of 3.3 days. 55 When tumor-specific folate functionalization was added, the particles' in vivo lifetime was extended to 12 days. 55 To increase the likelihood of sUPE transition with the TULSA device, a treatment arm combining sUPEs with Optison microbubbles was explored.…”

“…55 When tumor-specific folate functionalization was added, the particles' in vivo lifetime was extended to 12 days. 55 To increase the likelihood of sUPE transition with the TULSA device, a treatment arm combining sUPEs with Optison microbubbles was explored. Ultrasound exposure of microbubbles induces strong cavitation activity.…”

Perfluorocarbon-loaded polydopamine nanoparticles as ultrasound contrast agents

“…6 The large size of current ultrasound contrast agents (1–5 μm) is advantageous because it allows for high PFC-loading; however, it also restricts particle circulation time, displays poor accumulation and retention in target tissues, and only generates strong contrast at low frequencies, thus limiting resolution. 6 To improve upon these properties, a range of inorganic ultrasound contrast agents have been developed with better size control including hollow/porous silica, 1, 7–15 carbon nanotubes, 16 calcium carbonate nanoparticles, 17 and others. 18, 19 The rigid shell structure of these materials allows for robust particles of sub-micron diameter and can encapsulate PFC in a more stable fashion.…”