Prolonging the Ultrasound Signal Enhancement From Thrombi Using Targeted Microbubbles Based on Sulfur-Hexafluoride–Filled Gas

Bing, Wang; Zang, Wei-Jin; Wang, Mei; Ai, Hong; Wang, Yawen; Li, Yiping; He, Guangbin; Wang, Li; Yu, Xiaojiang

doi:10.1016/j.acra.2005.11.035

Cited by 22 publications

(15 citation statements)

References 25 publications

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“…Note better visualization of intravascular thrombus with targeted microbubbles. Reprinted with permission from Wang et al, Acad Radiol, Vol 13: 428-433, 2006 74 .…”

Section: Figurementioning

confidence: 99%

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Molecular ultrasound imaging: current status and future directions

2010

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Targeted contrast-enhanced ultrasound (molecular ultrasound) is an emerging imaging strategy that combines ultrasound technology with novel molecularly-targeted ultrasound contrast agents for assessing biological processes at the molecular level. Molecular ultrasound contrast agents are nano- or micro-sized particles that are targeted to specific molecular markers by adding high-affinity binding ligands onto the surface of the particles. Following intravenous administration, these targeted ultrasound contrast agents accumulate at tissue sites overexpressing specific molecular markers, thereby enhancing the ultrasound imaging signal. High spatial and temporal resolution, real-time imaging, non-invasiveness, relatively low costs, lack of ionizing irradiation and wide availability of ultrasound systems are advantages compared to other molecular imaging modalities. In this article we review current concepts and future directions of molecular ultrasound imaging, including different classes of molecular ultrasound contrast agents, ongoing technical developments of preclinical and clinical ultrasound systems , the potential of molecular ultrasound for imaging different diseases at the molecular level, and the translation of molecular ultrasound into the clinic.

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“…Note better visualization of intravascular thrombus with targeted microbubbles. Reprinted with permission from Wang et al, Acad Radiol, Vol 13: 428-433, 2006 74 .…”

Section: Figurementioning

confidence: 99%

“…These targeted agents were synthesized by adding Platelet glycoprotein (GP) IIb/IIIa receptor-targeted peptides onto the microbubble shell. A similar study used microbubbles with GP IIb/IIIa targeted peptides for imaging thrombi in femoral veins of dogs 74 . (Figure 8).…”

Section: Introductionmentioning

confidence: 99%

Molecular ultrasound imaging: current status and future directions

2010

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“…Intravenous MRX-802 combined with a diagnostic transthoracic US rapidly improved microvascular flow to the risk area and epicardial recanalization rates. Our previous studies have shown that the novel TMB-loading P1 polypeptide has high echogenicity, stability and good targeting to the thrombus in vivo [14], and when combined with LFUS, it is effective for thrombolysis in a 0.5 h cerebral embolism rabbit model without the risk of hemorrhage [15].…”

Section: Discussionmentioning

confidence: 99%

“…The TMB and UTMB were prepared as described previously [14,15]. In brief, TMB was a product of an oligopeptide (P1 polypeptide) specific to the glycoprotein IIb/ IIIa receptor on active platelets during a chemical reaction with dipalmitoylphosphatidylethanolamine (DPPG; Avanti Polar Lipids, Alabaster, AL, USA) and distearoylphosphatidylethanolamine-polyethylene glycol-benzotriazole carbonate (MW = 3400) (DSPE-PEG-BTC, Shearwater Polymers, Huntsville, AL, USA) (DPPG: DSPE-PEG-BTC: peptide = 73:21:6, wt/wt).…”

Section: Methodsmentioning

confidence: 99%

“…However, these TMBs were mainly used for US imaging rather than thrombolytic therapy. In our previous studies, a novel TMB was prepared via loading P 1 polypeptide as a new inhibitor of the GPIIb/IIIa receptor and was confirmed to have high echogenicity, stability and good targeting to thrombus in vivo [14]. When combined with external low-frequency ultrasound (LFUS), this novel TMB was effective not only in dissolving thrombus and recanalizing an occluded vessel in a 0.5 h cerebral embolism rabbit model [15] but also in preventing rethrombosis in vivo [16].…”

Section: Introductionmentioning

confidence: 96%

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Thrombolytic effects of a combined therapy with targeted microbubbles and ultrasound in a 6 h cerebral thrombosis rabbit model

Ren

Long

Wang

et al. 2011

J Thromb Thrombolysis

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Our previous study has shown that P1 polypeptide-loaded microbubbles (clot-targeted microbubbles, TMB) are effective for thrombolysis and recanalization in a 0.5 h cerebral thrombosis rabbit model when combined with low-frequency ultrasound (LFUS, 0.8 MHz). However, the thrombolytic effects of TMB combined with LFUS are still unclear in a 6 h cerebral thrombosis rabbit model, which closely resembles human embolic stroke. Aiming to extend the 3 h therapeutic window limitation of thrombolytic drugs, a 6 h cerebral thrombosis model of common carotid artery (CCA) occlusion was induced in rabbits, and thrombolysis using TMB by intra-arterial (IA) and intravenous (IV) application combined with LFUS was then compared to untargeted microbubbles (UTMB) and recombinant tissue plasminogen activator (rt-PA). The patency score and thrombolysis in brain ischemia (TIBI) in IA TMB combined with LFUS (IA TMB/LFUS) were significantly higher compared to the IA normal saline control with LFUS (IA SC/LFUS) (both P < 0.05) and IA UTMB plus LFUS (IA UTMB/LFUS) (both P < 0.05), respectively. The recanalization rate in the IA TMB/LFUS group (66.67%) was significantly higher compared to the IA SC/LFUS group (12.50%, P < 0.05). The patency score, TIBI and recanalization rate of IA TMB/LFUS were higher than in the IV TMB/LFUS group, but there was no significant difference between the two groups, which was similar to the infarction ratio. TMB/LFUS is an effective and safe therapy for thrombolysis in a 6 h cerebral thrombosis rabbit model, and the IA TMB/LFUS group was slightly better than the IV TMB/LFUS group.

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Intravital microscopy of localized stem cell delivery using microbubbles and acoustic radiation force

Kokhuis

Skachkov

Naaijkens

et al. 2014

Biotech & Bioengineering

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The use of stem cells for the repair of damaged cardiac tissue after a myocardial infarction holds great promise. However, a common finding in experimental studies is the low number of cells delivered at the area at risk. To improve the delivery, we are currently investigating a novel delivery platform in which stem cells are conjugated with targeted microbubbles, creating echogenic complexes dubbed StemBells. These StemBells vibrate in response to incoming ultrasound waves making them susceptible to acoustic radiation force. The acoustic force can then be employed to propel circulating StemBells from the centerline of the vessel to the wall, facilitating localized stem cell delivery. In this study, we investigate the feasibility of manipulating StemBells acoustically in vivo after injection using a chicken embryo model. Bare stem cells or unsaturated stem cells (<5 bubbles/cell) do not respond to ultrasound application (1 MHz, peak negative acoustical pressure P_ = 200 kPa, 10% duty cycle). However, stem cells which are fully saturated with targeted microbubbles (>30 bubbles/cell) can be propelled toward and arrested at the vessel wall. The mean translational velocities measured are 61 and 177 μm/s for P- = 200 and 450 kPa, respectively. This technique therefore offers potential for enhanced and well-controlled stem cell delivery for improved cardiac repair after a myocardial infarction.

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Prolonging the Ultrasound Signal Enhancement From Thrombi Using Targeted Microbubbles Based on Sulfur-Hexafluoride–Filled Gas

Cited by 22 publications

References 25 publications

Molecular ultrasound imaging: current status and future directions

Molecular ultrasound imaging: current status and future directions

Thrombolytic effects of a combined therapy with targeted microbubbles and ultrasound in a 6 h cerebral thrombosis rabbit model

Intravital microscopy of localized stem cell delivery using microbubbles and acoustic radiation force

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