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Materials and methods relating to cardiovascular imaging

A cardiovascular, imaging technique used in the field of disease progression and response to therapy, assessment of plaque burden and instability

Inactive Publication Date: 2014-01-01
伦敦王室学院
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

However, even with advances in the design of high-relaxation contrast agents, sensitivity remains a major limiting factor for molecular MRI compared to positron emission tomography, single photon emission computed tomography, and optical imaging

Method used

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  • Materials and methods relating to cardiovascular imaging
  • Materials and methods relating to cardiovascular imaging
  • Materials and methods relating to cardiovascular imaging

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Experimental program
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Embodiment Construction

[0033] Tropoelastin-specific or lysyl oxidase-specific binding agents

[0034] Tropoelastin is a matrix protein that is synthesized to form part of the walls of blood vessels. After expressing immature tropoelastin, it is covalently cross-linked to structurally mature elastin by the enzyme, lysyl oxidase (LOX) ( figure 1), which provide tensile strength to the vessel wall. Therefore, the present invention relates to conjugates capable of distinguishing (especially in vivo) de novo synthesized tropoelastin from mature cross-linked elastin, the former being associated with increased risk of plaque instability and rupture, which leads to AMI and / or stroke and / or aortic aneurysm. The sequences of human tropoelastin, lysyl oxidase, and elastin are available in sequence databases, along with corresponding polypeptide sequences in animal models (eg, rabbit) (see also the Sequences section below). Tropoelastin from other species can also be used to design specific binding peptides...

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Abstract

The invention provides conjugates for imaging plaques, such as cardiovascular plaques, as well as associated pharmaceutical compositions. Other aspects of the invention include methods for administering and imaging such conjugates and compositions, and using the imaging to characterise plaques. The conjugates of the invention distinguish between tropoelastin and elastin in plaques. The presence of tropoelastin can act as an indication that a plaque is liable to rupture or erode. Such information allows assessment of disease progression and response to treatment.

Description

technical field [0001] The present invention relates to materials and methods related to plaque imaging, and more particularly, to imaging cardiovascular plaques using agents capable of imaging plaques to assess plaque burden and instability, disease progression, and response to therapy . Background technique [0002] Acute myocardial infarction (AMI) and stroke remain the leading causes of death and morbidity in Western countries. AMI is primarily caused by rupture or erosion of unstable / fragile atherosclerotic plaques. A complex cluster of biological processes is involved in plaque progression and destabilization, including endothelial dysfunction, inflammation, neovascularization, outward remodeling, and breakdown of the extracellular matrix. Similarly, the development and rupture of aortic aneurysms is seen as a result of inflammation and stromal degeneration. [0003] Assessment of plaque burden and instability, disease progression and assessment of response to treat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/14A61K49/00C07K7/06C07K7/08
CPCG01N2800/32G01N2800/50C07K14/47A61K49/085C07K2319/61A61K49/14C07K5/1021A61K49/0002A61K51/088
Inventor 勒内·博特纳里阿尔季斯蒂斯·菲尼卡里斗
Owner 伦敦王室学院
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