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Detection reagent of atherosclerosis and preparation method thereof

A technology for detection of atherosclerosis and reagents, applied in the fields of biotechnology and clinical diagnosis, can solve the problems of not reflecting plaque vulnerability well, increased metabolic activity, false positives and false negatives, etc. The effect of high inflammation and low inflammation

Active Publication Date: 2018-09-04
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In recent years, researchers have attempted to apply 18 F-FDG PET examination has penetrated the examination of atherosclerosis to the cellular level, and reflects the inflammatory activity of the plaque through the increase of glucose uptake by macrophages and the increase of metabolic activity. 18 F-FDG is also taken up in the muscular layer of the blood vessel wall and surrounding tissues, and the increased metabolic activity of macrophages can also be caused by a large amount of phagocytosis of cholesterol, which does not necessarily reflect the activities related to plaque rupture, and is prone to false positives and false positives. feminine
Furthermore, some researchers have adopted 18 Evaluation of F-NaF on atherosclerotic plaques, the study found that there were high levels of microcalcification, macrophages, apoptosis, and necrosis in plaques 18 Uptake of F-NaF, a poor reflection of plaque vulnerability

Method used

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  • Detection reagent of atherosclerosis and preparation method thereof
  • Detection reagent of atherosclerosis and preparation method thereof
  • Detection reagent of atherosclerosis and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0052] Example 1. Synthesis of Polypeptide Derivative-like Atherosclerosis Detection Reagents

[0053] Taking a specific detection reagent compound of the present invention as an example, its synthesis steps are as follows:

[0054] (1) The derivative polypeptide sequence (Fmoc-Pip-Lys(Boc)-Lys-(Boc)-Arg(Pbf)-Pro-Hyp) protected by Fmoc was synthesized on 2-chlorotrityl chloride resin by solid-phase synthesis method (tBu)-Gly-Cpg-Ser(tBu)-D-Tic-Cpg). The resin was treated with 20% piperidine / DMF to remove the Na-Fmoc protecting group. 4-(Bromomethyl)phenylacetic acid (3 equiv) was activated with N,N'-diisopropylcarbodiimide (3 equiv) in 5 mL of N-methyl-2-pyrrolidone and then coupled to N- end. Subsequently, 1,4,7-triazacyclononane-1,4-bis(tert-butyl acetate) (3 equiv.) was alkylated by secondary amine in 5 mL of N-methyl-2-pyrrolidone Coupled to a polypeptide sequence. The polypeptide was cleaved from the resin with 95% TFA, and the synthesized polypeptide was purified by...

Embodiment 2

[0057] Embodiment two, stability analysis

[0058] Stability is an important indicator of in vivo diagnostic reagents. The detection reagents prepared in Example 1 were incubated in phosphate buffer and mouse serum at 37°C for 5, 15, 30, 60, and 120 minutes, and quenched with 70% acetonitrile at the end. Inactivated and centrifuged for 20 minutes, the stability of the polypeptide was determined by radioactive HPLC. The stability of the polypeptide in phosphate buffer saline and mouse serum can maintain at least two half-lives, indicating that the polypeptide has good stability.

Embodiment 3

[0059] Example 3. Specific identification of easily exfoliated plaques of atherosclerosis

[0060] Feeding ApoE knockout mice with high-fat diet is a common way to construct atherosclerosis model. After ApoE- / - mice were fed high-fat diet for 40 weeks, routine methods were used to identify high-risk atherosclerosis (easy shedding, low calcification) individuals and low-risk atherosclerosis (hard shedding, high calcification) individuals. 7.4 MBq of the detection reagent prepared in Example 1 was injected through the tail vein, and PET / CT imaging was performed 20 minutes later. image 3 The CT and PET / CT imaging results are given, showing that the polypeptide has high radioactive signal at the easily exfoliated plaque, but almost no radioactive signal at the calcified plaque visible on CT, realizing the anti-exfoliative plaque of atherosclerosis specific identification.

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PUM

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Abstract

The invention relates to a polypeptide derivative which specifically binds to atherosclerotic plaques. A detection reagent assesses the degree of risk of cerebral apoplexy caused by falling of the atherosclerotic plaques. The invention further provides a preparation method and application of the detection reagent.

Description

technical field [0001] The present invention relates to the fields of biotechnology and clinical diagnosis, in particular to the radioactivity detection of diseases by using polypeptide derivatives, and more specifically to a detection reagent for atherosclerosis, a preparation method and an application. Background technique [0002] Stroke is currently the most important cause of death from major diseases among urban and rural residents in my country, and carotid atherosclerosis is an important risk factor for stroke. Carotid plaque shedding plays a more critical role in ischemic cerebrovascular disease than carotid artery stenosis due to its size. The current non-invasive imaging methods for evaluating carotid plaque shedding include carotid ultrasound, contrast-enhanced ultrasound, transcranial Doppler ultrasound, CT angiography, and high-resolution MRI, which can observe the morphological changes of blood vessels, blood vessels, and blood vessels from the organ and tissu...

Claims

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Application Information

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IPC IPC(8): A61K51/08A61K49/04C07D255/02A61K101/02
CPCA61K49/04A61K51/08C07D255/02
Inventor 刘志博徐扬何洋张俊
Owner PEKING UNIV
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