scholarly journals Intracellular Vesicle Entrapment of Nanobubble Ultrasound Contrast Agents Targeted to PSMA Promotes Prolonged Enhancement and Stability In Vivo and In Vitro

2021 ◽  
Author(s):  
Reshani Perera ◽  
Eric Abenojar ◽  
Pinunta Nittayacharn ◽  
Xinning Wang ◽  
Gopal Ramamurthy ◽  
...  
Keyword(s):  
Contrast Agents ◽  
Ultrasound Contrast Agents ◽  
Therapeutic Interventions ◽  
Active Targeting ◽  
Target Cells ◽  
Acoustic Activity ◽  
Ultrasound Contrast ◽  
Imaging Plane

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.

Characteristics and Echogenicity of Clinical Ultrasound Contrast Agents: An In Vitro and In Vivo Comparison Study

2017 ◽  
Vol 36 (5) ◽  
pp. 941-953 ◽  
Author(s):  
Jean-Marc Hyvelin ◽  
Emmanuel Gaud ◽  
Maria Costa ◽  
Alexandre Helbert ◽  
Philippe Bussat ◽  
...  
Keyword(s):  
Contrast Agents ◽  
Ultrasound Contrast Agents ◽  
Comparison Study ◽  
Ultrasound Contrast

Effect of Bubble Concentration on the in Vitro and in Vivo Performance of Highly Stable Lipid Shell-Stabilized Micro- and Nanoscale Ultrasound Contrast Agents

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

scholarly journals Recent Experiences and Advances in Contrast-Enhanced Subharmonic Ultrasound

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
John R. Eisenbrey ◽  
Anush Sridharan ◽  
Ji-Bin Liu ◽  
Flemming Forsberg
Keyword(s):  
Contrast Agents ◽  
Tumor Imaging ◽  
Three Dimensional ◽  
Ultrasound Contrast Agents ◽  
Surrounding Tissue ◽  
Contrast Enhanced Ultrasound ◽  
Ultrasound Contrast ◽  
Contrast Enhanced ◽  
Subharmonic Response

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.

Stabilized bubbles in the body: pressure-radius relationships and the limits to stabilization

1997 ◽  
Vol 82 (6) ◽  
pp. 2045-2053 ◽  
Author(s):  
Hugh D. Van Liew ◽  
Soumya Raychaudhuri
Keyword(s):  
Contrast Agents ◽  
Conceptual Framework ◽  
Bubble Radius ◽  
Ultrasonic Imaging ◽  
Ultrasound Contrast Agents ◽  
The Body ◽  
Strong Growth ◽  
Ultrasound Contrast ◽  
Practical Usefulness

Van Liew, Hugh D., and Soumya Raychaudhuri. Stabilized bubbles in the body: pressure-radius relationships and the limits to stabilization. J. Appl. Physiol.82(6): 2045–2053, 1997.—We previously outlined the fundamental principles that govern behavior of stabilized bubbles, such as the microbubbles being put forward as ultrasound contrast agents. Our present goals are to develop the idea that there are limits to the stabilization and to provide a conceptual framework for comparison of bubbles stabilized by different mechanisms. Gases diffuse in or out of stabilized bubbles in a limited and reversible manner in response to changes in the environment, but strong growth influences will cause the bubbles to cross a threshold into uncontrolled growth. Also, bubbles stabilized by mechanical structures will be destroyed if outside influences bring them below a critical small size. The in vivo behavior of different kinds of stabilized bubbles can be compared by using plots of bubble radius as a function of forces that affect diffusion of gases in or out of the bubble. The two ends of the plot are the limits for unstabilized growth and destruction; these and the curve’s slope predict the bubble’s practical usefulness for ultrasonic imaging or O2 carriage to tissues.

Generation, application and quantification of clamp–BioShuttle carriers for plasmid delivery into nuclei of prostate cancer cells

2007 ◽  
Vol 35 (4) ◽  
pp. 829-832 ◽  
Author(s):  
R. Pipkorn ◽  
W. Waldeck ◽  
J.W. Jenne ◽  
B. Didinger ◽  
K. Braun
Keyword(s):  
Contrast Agents ◽  
Genetic Material ◽  
Target Cells ◽  
Prostate Cancer Cells ◽  
Delivery Vehicle ◽  
Active Materials ◽  
Diagnostic Agents ◽  
Plasmid Delivery

This paper presents the BioShuttle platform as a delivery vehicle for transfer of contrast agents and genetic material into target cells, which can be followed by activation of the BioShuttle inside the target cell. Here, we present a transporter system and summarize the findings on transporter use in vivo and in vitro. The results here are limited to examples where cargoes (drugs, genetically active materials or contrast agents) are covalently associated with the transporter module. A further example, in which the cargo is non-covalently attached to the BioShuttle, is also discussed. Finally, attempts have been made to solve some of the issues surrounding the efficiency of transfer of therapeutic or diagnostic agents and their later activity in the cell.

Temperature monitoring using ultrasound contrast agents: in vitro investigation on thermal stability

Ultrasonics ◽  
2004 ◽  
Vol 42 (1-9) ◽  
pp. 927-930 ◽  
Author(s):  
C Guiot ◽  
R Cavalli ◽  
P Gaglioti ◽  
D Danelon ◽  
C Musacchio ◽  
...  
Keyword(s):  
Thermal Stability ◽  
Contrast Agents ◽  
Ultrasound Contrast Agents ◽  
Temperature Monitoring ◽  
Ultrasound Contrast ◽  
In Vitro Investigation
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