Abstract 2482: Fate of Targeted Ultrasound Contrast Agents After Endothelial Adhesion: A Time Course Study

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Shivani Bowry ◽  
Jianjun Wang ◽  
Sue Ottoboni ◽  
Tom Ottoboni ◽  
William R Wagner ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Ultrasound Imaging ◽  
Time Course ◽  
Time Window ◽  
Leukocyte Adhesion ◽  
Ultrasound Contrast Agents ◽  
Acoustic Properties ◽  
Targeted Ultrasound ◽  
Ultrasound Molecular Imaging ◽  
Time Course Study

Background: Targeted microsphere (μSPH) adhesion to endothelial epitopes forms the basis for ultrasound molecular imaging. The fate of targeted μSPH, once bound to the endothelial target, is unknown. This has limited the optimization of ultrasound imaging strategies; for example, the appropriate time to commence imaging after μSPH injection is uncertain, and in part depends on the time course and duration of μSPH binding. We therefore sought to characterize the behavior of adhered μSPH as a function of time using serial observations of rat cremaster microcirculation after μSPH injection. Methods: Fluorescent nitrogen-encapsulated polymer μSPH (diameter 3.0 ± 1.4 μm) bearing control non-specific IgG (μSPH CTL ) or monoclonal antibody against VCAM (μSPH VCAM ) or ICAM (μSPH ICAM ) were prepared. Inflamed cremaster muscle of 21 anesthetized Wistar rats was exteriorized for intravital microscopy 4 hours after intrascrotal injection of TNF-α (5μg). Each rat received 1 venous injection of a single μSPH species (n=7 rats/μSPH; 10 8 μSPH/injection). An index venule was identified for serial microscopic observation every 5 min starting 10 min after μSPH injection. Results: The cumulative sum of adhered μSPH during 1 hr observation was higher for μSPH ICAM (24±11) and μSPH VCAM (18±1) than μSPH CTL (3±2, p=0.005). The number of μSPH ICAM adherent to the index venule was stable over time (10 min: 2 ± 3; 30 min: 3±2; 80 min: 3 ± 5, ANOVA p=0.9). The number of adhered μSPH VCAM trended downwards (10 min: 5±4; 30 min: 2±2; 80 min: 1±2; ANOVA p=0.08). By 1 hr, adhered μSPH appeared altered in shape; no μSPH transmigration was seen. Conclusions: Nitrogen-filled polymer μSPH targeted to leukocyte adhesion molecules adhere to inflamed endothelium. The extent of μSPH adhesion remains relatively constant over a time period relevant for imaging applications, although beyond 1hr, the μSPH appear morphologically altered and could have different acoustic properties. These data provide a useful and broad time window for effective ultrasound imaging of molecular targets. The time course of μSPH attachment to endothelium is an important consideration when devising strategies for ultrasound molecular imaging and should be characterized in a μSPH- and target- specific manner.

scholarly journals Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy

2015 ◽  
Vol 31 (2) ◽  
pp. 90-106 ◽  
Author(s):  
Tom van Rooij ◽  
Verya Daeichin ◽  
Ilya Skachkov ◽  
Nico de Jong ◽  
Klazina Kooiman
Keyword(s):  
Molecular Imaging ◽  
Contrast Agents ◽  
Ultrasound Contrast Agents ◽  
Ultrasound Contrast ◽  
Targeted Ultrasound ◽  
Ultrasound Molecular Imaging

scholarly journals Intracolic ultrasound molecular imaging: a novel method for assessing colonic tumor necrosis factor-α expression in inflammatory bowel disease

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Xiaoyan Miao ◽  
Ren Mao ◽  
Yujia You ◽  
Huichao Zhou ◽  
Chen Qiu ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Ultrasound Imaging ◽  
Intestinal Mucosa ◽  
Tumor Necrosis ◽  
Regression Analyses ◽  
Targeted Ultrasound ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Ultrasound Molecular Imaging ◽  
Necrosis Factor

Abstract Background While anti-tumor necrosis factor alpha (TNF-α) therapy has been proven effective in inflammatory bowel disease (IBD), approximately 40% of patients lose the response. Transmembrane TNF-α (mTNF-α) expression in the intestinal mucosa is correlated with therapeutic efficacy, and quantification of mTNF-α expression is significant for predicting response. However, conventional intravenous application of microbubbles is unable to assess mTNF-α expression in intestinal mucosa. Herein, we proposed intracolic ultrasound molecular imaging with TNF-α-targeted microbubbles (MBTNF-α) to quantitatively detect mTNF-α expression in the intestinal mucosa. Methods MBTNF-α was synthesized via a biotin–streptavidin bridging method. TNF-α-targeted ultrasound imaging was performed by intracolic application of MBTNF-α to detect mTNF-α expression in surgical specimens from a murine model and patients with IBD. Linear regression analyses were performed to confirm the accuracy of quantitative targeted ultrasound imaging. Results On quantitative TNF-α-targeted ultrasound images, a greater signal intensity was observed in the mouse colons with colitis ([1.96 ± 0.45] × 106 a.u.) compared to that of the controls ([0.56 ± 0.21] × 106 a.u., P < 0.001). Targeted US signal intensities and inflammatory lesions were topographically coupled in mouse colons. Linear regression analyses in specimens of mice and patients demonstrated significant correlations between the targeted ultrasound signal intensity and mTNF-α expression (both P < 0.001). Furthermore, TNF-α-targeted ultrasound imaging qualitatively distinguished the varying inflammatory severity in intestinal specimens from IBD patients. Conclusion Intracolic ultrasound molecular imaging with MBTNF-α enables quantitative assessment of mTNF-α expression. It may be a potential tool for facilitating the implementation of personalized medicine in IBD.

scholarly journals The Impact of Lipid Handling and Phase Distribution on the Acoustic Behavior of Microbubbles

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 119
Author(s):  
Simone A.G. Langeveld ◽  
Inés Beekers ◽  
Gonzalo Collado-Lara ◽  
Antonius F. W. van der Steen ◽  
Nico de Jong ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Molecular Imaging ◽  
High Speed ◽  
Phase Distribution ◽  
Direct Method ◽  
Ultrasound Contrast Agents ◽  
Lipid Phase ◽  
Acoustic Behavior ◽  
Ultrasound Molecular Imaging ◽  
The Impact

Phospholipid-coated microbubbles are ultrasound contrast agents that can be employed for ultrasound molecular imaging and drug delivery. For safe and effective implementation, microbubbles must respond uniformly and predictably to ultrasound. Therefore, we investigated how lipid handling and phase distribution affected the variability in the acoustic behavior of microbubbles. Cholesterol was used to modify the lateral molecular packing of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)-based microbubbles. To assess the effect of lipid handling, microbubbles were produced by a direct method, i.e., lipids directly dispersed in an aqueous medium or indirect method, i.e., lipids first dissolved in an organic solvent. The lipid phase and ligand distribution in the microbubble coating were investigated using confocal microscopy, and the acoustic response was recorded with the Brandaris 128 ultra-high-speed camera. In microbubbles with 12 mol% cholesterol, the lipids were miscible and all in the same phase, which resulted in more buckle formation, lower shell elasticity and higher shell viscosity. Indirect DSPC microbubbles had a more uniform response to ultrasound than direct DSPC and indirect DSPC-cholesterol microbubbles. The difference in lipid handling between direct and indirect DSPC microbubbles significantly affected the acoustic behavior. Indirect DSPC microbubbles are the most promising candidate for ultrasound molecular imaging and drug delivery applications.

VEGFR2-Targeted Ultrasound Molecular Imaging of Angiogenesis to Evaluate Liver Allograft Fibrosis

2021 ◽  
Author(s):  
Chen Qiu ◽  
Tingting Sha ◽  
Tinghui Yin ◽  
Wei Zhang ◽  
Xiuling Chen ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Liver Allograft ◽  
Targeted Ultrasound ◽  
Ultrasound Molecular Imaging

Hydrodynamics and Leukocyte Adhesion in Microvessels: State of the Art

2008 ◽  
Author(s):  
Josa Hanzlik ◽  
Ellen Cretekos ◽  
Kathleen A. Lemkin-Kennard
Keyword(s):  
Leukocyte Adhesion ◽  
Ultrasound Contrast Agents ◽  
Great Promise ◽  
Computational Techniques ◽  
Leukocyte Rolling ◽  
Complex Flow ◽  
Nano Fabrication ◽  
Physiological Processes ◽  
Targeted Ultrasound ◽  
Novel Devices

Leukocyte rolling and adhesion are complex physiological processes that have received a great deal of attention over the past decade. Significant increases in the knowledge base related to how leukocytes adhere in shear flows have occurred as a result of the development of novel experimental and computational techniques. Micro- and nano-fabrication techniques have enabled the development of novel flow devices for studying leukocyte adhesion in simple and complex geometries. Improvements in computer technology have enabled simulations of complex flow processes to be developed. As a result of these advances in knowledge related to leukocyte adhesion, numerous novel devices have been developed that mimic the leukocyte rolling and adhesion process. Examples of these devices include cell separation and enrichment devices and targeted ultrasound contrast agents. Future advances related to leukocyte rolling and adhesion processes hold great promise for advancing our knowledge of disease processes as well as development of novel therapeutic devices.

scholarly journals Thyroid Cancer Detection by Ultrasound Molecular Imaging with SHP2-Targeted Perfluorocarbon Nanoparticles

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
ZhongQian Hu ◽  
Bin Yang ◽  
Tiankuan Li ◽  
Jia Li
Keyword(s):  
Thyroid Cancer ◽  
Molecular Imaging ◽  
Diagnostic Accuracy ◽  
Protein Tyrosine Phosphatases ◽  
Ultrasound Contrast Agents ◽  
Human Thyroid ◽  
Thyroid Tumour ◽  
Ultrasound Molecular Imaging

Background. Contrast-enhanced ultrasound imaging has been widely used in the ultrasound diagnosis of a variety of tumours with high diagnostic accuracy, especially in patients with hepatic carcinoma, while its application is rarely reported in thyroid cancer. The currently used ultrasound contrast agents, microbubbles, cannot be targeted to molecular markers expressed in tumour cells due to their big size, leading to a big challenge for ultrasound molecular imaging. Phase-changeable perfluorocarbon nanoparticles may resolve the penetrability limitation of microbubbles and serve as a promising probe for ultrasound molecular imaging. Methods. 65 thyroid tumour samples and 40 normal samples adjacent to thyroid cancers were determined for SHP2 expression by IHC. SHP2-targeted PLGA nanoparticles (NPs-SHP2) encapsulating perfluoropentane (PFP) were prepared with PLGA-PEG as a shell material, and their specific target-binding ability was assessed in vitro and in vivo, and the effect on the enhancement of ultrasonic imaging induced by LIFU was studied in vivo. Results. In the present study, we verified that tumour overexpression of SHP2 and other protein tyrosine phosphatases regulated several cellular processes and contributed to tumorigenesis, which could be introduced to ultrasound molecular imaging for differentiating normal from malignant thyroid diagnostic nodes. The IHC test showed remarkably high expression of SHP2 in human thyroid carcinoma specimens. In thyroid tumour xenografts in mice, the imaging signal was significantly enhanced by SHP2-targeted nanoparticles after LIFU induction. Conclusion. This study provides a basis for preclinical exploration of ultrasound molecular imaging with NPs-SHP2 for clinical thyroid nodule detection to enhance diagnostic accuracy.

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