Molecular Imaging of Human Thrombus With Novel Abciximab Immunobubbles and Ultrasound

Alonso, Angelika; Martina, Alberto Della; Stroick, Mark; Fatar, Marc; Griebe, Martin; Pochon, Sibylle; Schneider, Michel; Hennerici, Michael G.; Allémann, Éric; Meairs, Stephen

doi:10.1161/strokeaha.106.471391

Cited by 119 publications

(73 citation statements)

References 23 publications

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“…Role of other advanced imaging techniques like photoacoustic imaging (81), biotechnology/nanotechnology is being investigated (82,83) in diagnosing and estimating age and monitoring treatment of DVT (84).…”

Section: Scintigraphymentioning

confidence: 99%

Advanced imaging in acute and chronic deep vein thrombosis

Karande

Hedgire

Sánchez

et al. 2016

Cardiovasc. Diagn. Ther.

108

107

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Section: Scintigraphymentioning

confidence: 99%

Advanced imaging in acute and chronic deep vein thrombosis

Karande

Hedgire

Sánchez

et al. 2016

Cardiovasc. Diagn. Ther.

108

107

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“…Fibrin-containing blood clots have been extensively used as a target for site-specific delivery of imaging agents and anticlotting agents to thrombi (8)(9)(10). Delivering anticoagulants into vessels where clotting is taking place has been shown to be effective at reducing the formation and expansion of clots, and it also decreases the risk of systemic side effects (11,12).…”

Section: Ardiovascular Disease Affects 1 In 3 People In the Unitedmentioning

confidence: 99%

Targeting atherosclerosis by using modular, multifunctional micelles

Peters

Kastantin

Kotamraju

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

257

252

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Subtle clotting that occurs on the luminal surface of atherosclerotic plaques presents a novel target for nanoparticle-based diagnostics and therapeutics. We have developed modular multifunctional micelles that contain a targeting element, a fluorophore, and, when desired, a drug component in the same particle. Targeting atherosclerotic plaques in ApoE-null mice fed a high-fat diet was accomplished with the pentapeptide cysteine-arginine-glutamic acid-lysine-alanine, which binds to clotted plasma proteins. The fluorescent micelles bind to the entire surface of the plaque, and notably, concentrate at the shoulders of the plaque, a location that is prone to rupture. We also show that the targeted micelles deliver an increased concentration of the anticoagulant drug hirulog to the plaque compared with untargeted micelles.cysteine-arginine-glutamic acid-lysine-alanine ͉ hirulog ͉ plaque ͉ imaging ͉ nanoparicles C ardiovascular disease affects 1 in 3 people in the United States during their lifetime, and accounts for nearly a third of the deaths that occur each year (1). Atherosclerosis is one of the leading causes of cardiovascular disease, and it results in raised plaques in the arterial wall that can occlude the vascular lumen and block blood flow through the vessel. Recently, it has become clear that not all plaques are the same. Those susceptible to rupture, fissuring, and subsequent thrombosis are most frequently the cause of acute coronary syndromes and death (2).Rupture of an atherosclerotic plaque exposes collagen and other plaque components to the bloodstream. This rupture initiates hemostasis in the blood vessel and leads to activation of thrombin and a thrombus to form at the site of rupture. Elevated levels of activated thrombin bound to the vessel wall have been observed up to 72 h after vascular injury (3). These elevated thrombin levels not only induce clot formation but also have been implicated in the progression of atherosclerosis by causing smooth muscle cells to bind circulating low density lipoprotein (4). Subtle clotting in plaques is also indicated by deposition of fibrin(ogen) both inside and on the surface of atherosclerotic plaques, which has been well documented since the 1940s (5-7).Fibrin-containing blood clots have been extensively used as a target for site-specific delivery of imaging agents and anticlotting agents to thrombi (8-10). Delivering anticoagulants into vessels where clotting is taking place has been shown to be effective at reducing the formation and expansion of clots, and it also decreases the risk of systemic side effects (11,12). Antibodies and peptides that bind to molecular markers specifically expressed on atherosclerotic plaques have shown promise for plaque imaging in vivo (13-16), but clotting on the plaque has not been used as a target. We reasoned that the fibrin deposited on plaques could serve as a target for delivering diagnostic and therapeutic compounds to plaques.We chose the clot-binding peptide cysteine-arginine-glutamic acid-lysine-alanine (CREKA) to te...

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“…Once all of the contrast agent in the blood pool has been washed out, specifically bound microbubbles remain detectable at the site of the target structure. Initially very promising results have demonstrated successful in vitro targeted imaging of human clots with abciximab immunobubbles [54]. A possible clinical application is the positive detection of thrombotic material either at the ICA plaque or in an occluded cerebral artery.…”

mentioning

confidence: 99%

“…Future developments could also generate additional targeted bubbles, e. g., for the detection of inflammation or angiogenesis. It has been speculated that the binding of targeted microbubbles to the thrombotic material could reduce possible side-effects of sonothrombolytic therapy [54]. Irrespective of this, another possible future application is the binding of therapeutic agents, e. g., thrombolytics, to the bubbles which could then be released by insonification at the site of vascular obstruction hence reducing systemic side-effects of the agent (ultrasound mediated drug delivery).…”

mentioning

confidence: 99%