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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  • Application Information

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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

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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[0084] Example 1

[0085] 1. Preparation of sterically stable liposomes

[0086] The liposome membrane material (DSPC / CHOL / mPEG-DSPE / Gd-DTPA-BSA) was dissolved in an appropriate amount of anhydrous chloroform and methanol mixed solvent (volume ratio 2:1) in a molar ratio of 36 / 36 / 3 / 25, 40 The solvent was removed by rotary evaporation at °C to prepare a lipid film, which was placed in a vacuum drying oven at room temperature overnight to remove traces of solvent. Add HEPES buffer (HBS, 20 mM HEPES, 135 mM NaCl, pH=6.5) in a certain ratio (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 nuclear pore membranes with pore diameters of 400 nm, 200 nm and 100 nm 10 times at a high pressure homogenizer at 60° C. 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...

Example Embodiment

[0110] Example 2 MR molecular imaging experiment of Endoglin target in rat glioma neovascular endothelial cells

[0111] Twenty-five established rat models of glioma in situ were randomly divided into 5 groups from A to E, with 5 rats in each group. -SLs), isotype control IgG liposomes (IgG-SLs), immunoliposome probes conjugated with Endoglin monoclonal antibody (MAb-SLs) for MR imaging, two-step prelocalization imaging Rats were pre-administered with biological Monoclonal antibody (Bio-MAb) was then administered with streptavidin liposome probes (SAv-SLs) for imaging; the differences in tumor enhancement performance on MR T1-weighted enhanced images of rats in each group were compared, and each group was analyzed. Time-signal enhancement characteristics of arterial blood vessels, normal brain tissue and muscle tissue, and tumor tissue; compare the differences in tumor enhancement degree and enhancement range among the groups, and compare the enhancement differences between th...

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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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