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Magnetic resonance imaging contrast agent as well as preparation method and application thereof

A magnetic resonance imaging and contrast agent technology, applied in the field of medical imaging, can solve the problems of instability of nanocomposites, easy disintegration, affecting the targeting of contrast agents, etc.

Inactive Publication Date: 2014-08-20
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The nanocomplex formed in it is unstable and easily disintegrated after being diluted by body fluids in vivo, thus affecting the targeting of contrast agents

Method used

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  • Magnetic resonance imaging contrast agent as well as preparation method and application thereof
  • Magnetic resonance imaging contrast agent as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Example 1 A magnetic resonance imaging contrast agent linked to nucleic acid aptamer GBI-10

[0062] The magnetic resonance imaging contrast agent consists of a 5' terminal amino-modified nucleic acid aptamer GBI-10 and gadolinium-loaded liposomes. The gadolinium-loaded liposome is composed of distearoylphosphatidylcholine (DSPC), cholesterol, gadolinium-diethylenetriaminepentaacetic acid-octadecylamine (Gd-DTPA-BSA), distearoylphosphatidylethanolamine -Polyethylene glycol 2000 (DSPE-mPEG 2000 ) and distearoylphosphatidylethanolamine-polyethylene glycol 2000-carboxyl cross-linked product (DSPE-PEG 2000 -COOH) composition. The 5' terminal amino group of the modified GBI-10 is linked to the carboxyl group of the polyethylene glycol chain of the distearoylphosphatidylethanolamine-polyethylene glycol 2000-carboxyl crosslinked product in the gadolinium-loaded liposome through an amide bond .

[0063] The magnetic resonance imaging contrast agent described in this embo...

Embodiment 2

[0066] Example 2 A fluorescent-labeled magnetic resonance imaging contrast agent linked to nucleic acid aptamer GBI-10

[0067] The magnetic resonance imaging contrast agent consists of a 5' terminal amino-modified nucleic acid aptamer GBI-10 and gadolinium-loaded liposomes. The gadolinium-loaded liposome is composed of distearoylphosphatidylcholine (DSPC), cholesterol, gadolinium-diethylenetriaminepentaacetic acid-octadecylamine (Gd-DTPA-BSA), distearoylphosphatidylethanolamine -Polyethylene glycol 2000 (DSPE-mPEG 2000 ), distearoylphosphatidylethanolamine-polyethylene glycol 2000-carboxyl cross-linked product (DSPE-PEG 2000 -COOH) and the fluorescent substance coumarin-6. The 5' terminal amino group of the modified GBI-10 is linked to the carboxyl group of the polyethylene glycol chain of the distearoylphosphatidylethanolamine-polyethylene glycol 2000-carboxyl crosslinked product in the gadolinium-loaded liposome through an amide bond .

[0068] The magnetic resonance...

Embodiment 3

[0072] Example 3 A magnetic resonance imaging contrast agent linked to nucleic acid aptamer GBI-10

[0073] The magnetic resonance imaging contrast agent is composed of a nucleic acid aptamer GBI-10 modified with 12 thymidylates at the 5' end and a liposome carrying gadolinium. The sequence of GBI-10 is: 5'-CCC AGA GGG AAG ACT TTA GGT TCG GTT CAC GTC C-3'. The gadolinium-loaded liposome is composed of hydrogenated soybean phospholipids (HSPC), cholesterol, gadolinium-diethylenetriaminepentaacetic acid-octadecylamine (Gd-DTPA-BSA) and distearoylphosphatidylethanolamine-polyethylene glycol Alcohol 2000 (DSPE-mPEG 2000 )composition. The hydroxyl group of the modified GBI-10 is connected with the hydroxyl group of the phosphorylated cholesterol in the gadolinium-loaded liposome through a phosphate bond.

[0074] The magnetic resonance imaging contrast agent described in this embodiment can be prepared by the following method:

[0075] 1. Link the modified GBI-10 to choleste...

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Abstract

The invention provides a magnetic resonance imaging contrast agent comprising a nucleic acid aptamer analogue and lipidosome of entrapping gadolinium, wherein the nucleic acid aptamer analogue is connected to the lipidosome of entrapping gadolinium by virtue of a chemical bond, and is selected from one or more of GBI-10, AS1411, A10, MUC1, sgc8, sgc3, sgd3, KHlCl, KDO5, S6, AGRO100, A30 and STRG2 modified by sulfydryl, amino or sites. The invention also provides a preparation method of the magnetic resonance imaging contrast agent, and application thereof in preparation of a tumor-targeted image detection preparation or a tumor-targeted treatment medicament. The magnetic resonance imaging contrast agent provided by the invention is stable in structure, the nucleic acid aptamer analogue is taken as a target head and oriented to a plurality of tumors, tumor cells can be discovered at an early stage, and the diagnosis and treatment effects are improved.

Description

technical field [0001] The invention belongs to the technical field of medical imaging, and in particular relates to a tumor-targeting magnetic resonance imaging contrast agent. Background technique [0002] At present, cancer is the disease with the second highest mortality rate in the world, seriously affecting human health. Early detection and diagnosis of tumor is particularly important to improve the effect of tumor treatment. [0003] Current methods used to detect tumors include: magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), ultrasound, single photon emission computed tomography (SPECT), and optical imaging, among others. Among them, CT, PET, and SPECT have ionizing radiation, which will cause certain harm to patients, especially when multiple inspections are performed; although ultrasonography is safe, it is highly dependent on the technology of inspectors; optical imaging has great limitations Sex, can only penetra...

Claims

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Application Information

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IPC IPC(8): A61K49/10A61K49/18A61K45/00A61K47/26A61K9/127A61P35/00
Inventor 范田园顾梦洁杨振军李昆峰张兰馨王欢郑卓肇
Owner PEKING UNIV
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