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Atherosclerosis detection reagent and preparation method thereof

An atherosclerosis and detection reagent technology, applied in the fields of biotechnology and clinical diagnosis, can solve the problems of not well reflecting plaque vulnerability, elevated metabolic activity, false positives and false negatives, etc. Effects of high and low levels of inflammation

Active Publication Date: 2020-10-27
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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  • Atherosclerosis detection reagent and preparation method thereof
  • Atherosclerosis detection reagent and preparation method thereof
  • Atherosclerosis detection reagent and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Example 1. Synthesis of polypeptide derivative atherosclerosis detection reagent

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

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

[0055] (...

Embodiment 2

[0057] Example 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. It was quenched and centrifuged for 20 minutes, and the stability of the polypeptide was determined by radio HPLC. The stability of the polypeptide in phosphate buffer 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 atherosclerotic plaque

[0060] Feeding ApoE knockout mice with high-fat diet is a common method to construct atherosclerosis models. After ApoE- / - mice were fed high-fat diet for 40 weeks, conventional methods were used to identify high-risk atherosclerosis (easy to fall off, low calcification) individuals and low-risk atherosclerosis (not easy to fall off, high calcification) individuals. The detection reagent 7.4MBq prepared in Example 1 was injected through the tail vein, and PET / CT imaging was performed 20 minutes later. image 3 The results of CT and PET / CT imaging are given, indicating that the polypeptide has high radiation signals at the plaques that are easy to fall off, but there is almost no radiation signal at the calcified plaques visible on CT, which realizes the treatment of atherosclerosis and easy fall off plaques. The specific identification.

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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 radioactive detection of diseases using polypeptide derivatives, and more specifically to an atherosclerosis detection reagent, preparation method and application. Background technique [0002] Stroke is currently the most important cause of deaths from major diseases in urban and rural residents in my country, and carotid atherosclerosis is an important risk factor for stroke. Carotid artery plaque shedding plays a more critical role in ischemic cerebrovascular disease than the degree of carotid artery stenosis due to its size. Current non-invasive imaging methods for evaluating carotid artery 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 and blood vessels at the organ and tissue level Flow dyna...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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