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Glioma-targeting molecule magnetic resonance contrast agent as well as preparation method and application thereof

A molecular magnetic resonance and glioma targeting technology, applied in the field of molecular imaging, can solve the problems of low non-specific binding, cumbersome operation, and large amount of avidin

Inactive Publication Date: 2012-02-15
AFFILIATED HUSN HOSPITAL OF FUDAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The advantage of the three-step method is that it can reduce the imaging interference in the circulating background and improve the local imaging contrast of the target, but its operation is cumbersome, and the amount of avidin is relatively large, which has obvious toxic effects
The molecular structures of the avidin (Avidin, Av) and streptavidin (Streptavidin, SAv) are similar, both have four identical subunits, and can bind to biotin with high specific affinity, but the chain Mycoavidin is a near-neutral protein and does not contain sugar groups, so it has low non-specific binding to charged molecules and cell membrane sugar receptors in vivo

Method used

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  • Glioma-targeting molecule magnetic resonance contrast agent as well as preparation method and application thereof
  • Glioma-targeting molecule magnetic resonance contrast agent as well as preparation method and application thereof
  • Glioma-targeting molecule magnetic resonance contrast agent as well as preparation method and application thereof

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Embodiment 1

[0085] 1. Preparation of sterically stable liposomes

[0086] Liposome membrane material (DSPC / CHOL / mPEG-DSPE / Gd-DTPA-BSA) is dissolved in appropriate amount of anhydrous chloroform and methanol mixed solvent (volume ratio 2: 1) by 36 / 36 / 3 / 25 molar ratio, 40 The solvent was removed by rotary evaporation at ℃, and the lipid film was prepared, and the trace solvent was removed overnight in a vacuum oven at room temperature. Add HEPES buffer (HBS, 20 mM HEPES, 135 mM NaCl, pH=6.5) in a certain proportion (100 μmol lipid: 3 ml), vortex vigorously, hydrate in a water bath at 60 ° C for 2 hours to form a lipid suspension. The suspension was sequentially extruded through a nuclear pore membrane with a pore size of 400 nm, 200 nm, and 100 nm in a high-pressure homogenizer at 60°C for 10 times each to obtain liposomes with a particle size of about 100-120 nm.

[0087] 2. Preparation of PDP-sterically stabilized liposomes (PDP-SLs)

[0088] The preparation method of the PDP-sterically...

Embodiment 2

[0110] Example 2 MR Molecular Imaging Experiment of Endoglin Targets in Rat Glioma Neovascular Endothelial Cells

[0111] 25 established rat orthotopic glioma animal models were randomly divided into 5 groups A-E, with 5 rats in each group, and injected gadopentetate dimeglumine (Gd-DTPA) and blank liposome (Gd-DTPA) into the tail vein respectively. -SLs), isotype control IgG liposomes (IgG-SLs), immunoliposome probes combined with Endoglin monoclonal antibody (MAb-SLs) for MR imaging, two-step pre-positioned imaging rats pre-administered biological Streptavidin liposome probes (SAv-SLs) were given after the primed monoclonal antibody (Bio-MAb) for imaging; the differences in tumor enhancement performance in MR T1-weighted enhanced images of rats in each group were compared, and the Time-signal enhancement characteristics of arteries, normal brain tissue, muscle tissue, and tumor tissue; compare the differences in the degree and range of tumor enhancement among the groups, and...

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Abstract

The invention belongs to the technical field of molecule imaging, and relates to a glioma-targeting molecule magnetic resonance contrast agent as well as a preparation method and an application thereof. The contrast agent comprises two complexes, namely a biotinylated monoclonal antibody and a streptavidin Gd-coated spatial stable immune liposome; and the two complexes are reacted and combined toform MAb-X-Y-Z-Gd. The experiment results show that: the molecular probe can combine with glioma neogenesis blood capillaries without passing through the blood-brain barrier while actively targeting the tumor neogenesis blood vessels, and an MRI (magnetic resonance imaging) signal is amplified by a biotin-avidin system, thereby achieving high-resolution glioma-specific targeting imaging; and the biotin-avidin-mediated two-step imaging method has effectivity, thereby proving a new nondestructive method for glioma early-stage diagnosis, the research of biological behavior, and anti-vessel survival treatment targeting and treatment effect evaluation.

Description

technical field [0001] The invention belongs to the technical field of molecular imaging, and relates to a glioma-targeting molecular magnetic resonance contrast agent, in particular to a glioma-targeting molecular magnetic resonance contrast agent and its preparation method and application, especially to an Endoglin target-based A two-step space-stabilized liposome magnetic resonance molecular contrast agent, a preparation method thereof, and an application in magnetic resonance molecular imaging; the contrast agent can actively target and specifically display brain glioma neovascularization. Background technique [0002] Glioma is the most common primary malignant tumor in the brain. According to statistics, there are 40,000 to 130,000 new cases of glioma each year in my country. The degree of malignancy is high, and it accounts for the fourth place in the death rate of systemic malignant tumors. At present, the preferred treatment for this disease is still surgery, but cl...

Claims

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Application Information

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IPC IPC(8): A61K49/16A61K49/10A61K49/18A61K103/34
Inventor 冯晓源邱龙华张家文陆伟跃姚振威李树平李安宁
Owner AFFILIATED HUSN HOSPITAL OF FUDAN UNIV
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