Use of radiation force for enhancing efficacy of molecular targeted ultrasound contrast agents ‐ in vitro and in vivo

2008 ◽  
Vol 123 (5) ◽  
pp. 3793-3793
Author(s):  
John A. Hossack
2017 ◽  
Vol 36 (5) ◽  
pp. 941-953 ◽  
Author(s):  
Jean-Marc Hyvelin ◽  
Emmanuel Gaud ◽  
Maria Costa ◽  
Alexandre Helbert ◽  
Philippe Bussat ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Arifudin Achmad ◽  
Aiko Yamaguchi ◽  
Hirofumi Hanaoka ◽  
Yoshito Tsushima

Shell thickness determines the acoustic response of polymer-based perfluorooctyl bromide (PFOB) nanocapsule ultrasound contrast agents. PEGylation provides stealth property and arms for targeting moieties. We investigated a modulation in the polymer formulation of carboxy-terminated poly(D,L-lactide-co-glycolide) (PLGA) and poly(D,L-lactide-co-glycolide)-block-polyethylene glycol (PLGA-b-PEG) to produce thin-shelled PFOB nanocapsules while keeping its echogenicity, stealth property, and active targeting potential. Polymer formulation contains 40% PLGA-PEG that yields the PEGylated PFOB nanocapsules of approximately 150 nm size with average thickness-to-radius ratio down to 0.15, which adequately hindered phagocytosis. Functionalization with antibody enables in vitro tumor-specific targeting. Despite the acoustic response improvement, the in vivo tumor accumulation was inadequate to generate an observable acoustic response to the ultrasound power at the clinical level. The use of PLGA and PLGA-PEG polymer blend allows the production of thin-shelled PFOB nanocapsules with echogenicity improvement while maintaining its potential for specific targeting.


Langmuir ◽  
2019 ◽  
Vol 35 (31) ◽  
pp. 10192-10202 ◽  
Author(s):  
Eric C. Abenojar ◽  
Pinunta Nittayacharn ◽  
Al Christopher de Leon ◽  
Reshani Perera ◽  
Yu Wang ◽  
...  

2021 ◽  
Author(s):  
Reshani Perera ◽  
Eric Abenojar ◽  
Pinunta Nittayacharn ◽  
Xinning Wang ◽  
Gopal Ramamurthy ◽  
...  

Previous work has shown that active targeting of nanobubble (NB) ultrasound contrast agents to the prostate-specific membrane antigen (PSMA) significantly prolongs ultrasound signal enhancement in PSMA-expressing prostate cancer. However, the specific mechanism behind this effect is not well understood. Furthermore, prior studies were carried out using clinical ultrasound scanners in a single imaging plane. Because tumor heterogeneity can have a drastic effect on bubble kinetics and resulting contrast enhancement, a single region of interest in one imaging plane over time may not fully represent the contrast dynamics of the entire tumor. Accordingly, in the current work, we used high-frequency dynamic parametric contrast-enhanced ultrasound (DCE-US) imaging to gain a detailed understanding of NB kinetics in prostate tumors in mice. Specifically, we examined the differences in enhancement between the tumor periphery and tumor core in the same imaging plane. We also quantified intact nanobubble retention in the entire tumor volume. To better understand the mechanism behind prolonged tumor enhancement, intracellular retention and the acoustic activity of PSMA-NB were evaluated in cell culture. DCE-US US data suggest that both tumor wash-in and retention of PSMA-NB are delayed due to biomarker interaction and binding. The longer retention of PSMA-NB signal in tumor core supported target-driven bubble extravasation. In vitro studies demonstrated a higher level of internalization and prolonged-acoustic activity of internalized PSMA-NB. GC/MS analysis confirmed gas persistence in the cells after PSMA-NB internalization. The active-targeting of NB results in cellular internalization via receptor-mediated endocytosis, and the location with intracellular vesicles (late-stage endosomes/lysosomes) significantly prolongs gas retention within the cells. These features can enable background-free diagnostic imaging of the target cells/tissues, as well as highly focused ultrasound-modulated therapeutic interventions.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
John R. Eisenbrey ◽  
Anush Sridharan ◽  
Ji-Bin Liu ◽  
Flemming Forsberg

Nonlinear contrast-enhanced ultrasound imaging schemes strive to suppress tissue signals in order to better visualize nonlinear signals from blood-pooling ultrasound contrast agents. Because tissue does not generate a subharmonic response (i.e., signal at half the transmit frequency), subharmonic imaging has been proposed as a method for isolating ultrasound microbubble signals while suppressing surrounding tissue signals. In this paper, we summarize recent advances in the use of subharmonic imagingin vivo. These advances include the implementation of subharmonic imaging on linear and curvilinear arrays, intravascular probes, and three-dimensional probes for breast, renal, liver, plaque, and tumor imaging.


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