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Gadolinium oxide targeted magnetic resonance contrast agent

A technology of magnetic resonance contrast agent and gadolinium oxide target, which is applied in the direction of emulsion delivery, drug delivery, preparations for in vivo tests, etc.

Inactive Publication Date: 2014-03-19
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But so far, no literature has reported Gd modified with target body 2 o 3 Nanoparticles used in imaging study of glioma

Method used

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  • Gadolinium oxide targeted magnetic resonance contrast agent
  • Gadolinium oxide targeted magnetic resonance contrast agent
  • Gadolinium oxide targeted magnetic resonance contrast agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] 1) Gd coated with oleic acid 2 o 3 Synthesis

[0063] oleic acid-coated Gd 2 o 3 The synthesis of is prepared by the known high-temperature reduction method, and the method has been slightly modified. Add 1.6g of oleic acid, 1.6g of oleylamine and 2mmol of gadolinium acetylacetonate into 20mL of benzyl ether, then extract the air and stir for 1h at 100°C under vacuum to remove moisture and air. Then, filled with nitrogen, the solution was heated to 290°C and maintained for 2.5h. After the reaction was completed and cooled to room temperature, the oleic acid-coated Gd 2 o 3 Precipitate with 20 mL of ethanol, collect the precipitate after centrifugation, wash the precipitate with ethanol three times, and disperse into 10 mL of n-hexane for later use.

[0064] 2) Water-soluble TETT-Gd 2 o 3 Preparation of nanoparticles

[0065] Water-soluble TETT-Gd 2 o 3 Nanoparticles are prepared by the ligand exchange method. 100mg Oleic Acid Encapsulated Gd 2 o 3 and 60 ...

Embodiment 2

[0075] Relaxation rate test results of nanoparticles

[0076] Prepare gained PEG-Gd in embodiment 1 2 o 3 , FA-PEG-Gd 2 o 3 FA-PEG-Gd on 7TMRI 2 o 3 The performance of nanoparticles as a potential MRI contrast enhancing agent was evaluated. The commercially available contrast agent Magnevist (Gd-DTPA) was used as a control. The relaxation rate (r1) is taken from the 1 / T1 relaxation time (s -1 ) and the slope of the Gd ion concentration (mM) curve. Such as Figure 4 shown, and the value of r1 for Gd-DTPA nanoparticles were estimated to be 8.33 mM -1 the s -1 , 4.48mM -1 the s -1 and 4.01mM -1 the s -1 . Apparently, PEG-Gd 2 o 3 , FA-PEG-Gd 2 o 3 Shows a higher relaxation rate r1 than Gd-DTPA.

Embodiment 3

[0078] In vivo imaging tests of nanoparticles

[0079] Prepare gained PEG-Gd in embodiment 1 2 o 3 , FA-PEG-Gd 2 o 3 Nanoparticles are used as a positive contrast agent for MRI research on brain gliomas. Such as Figure 5 Intravenous injection of PEG-Gd shown 2 o 3 and FA-PEG-Gd 2 o 3 Nanoparticles recorded T1-weighted images of mouse glioma at 7T nuclear magnetic resonance, respectively before and 15 minutes, 120 minutes and 24 hours after magnetic resonance image recording. The compound of each tail vein injection contains the Gd ion (0.1mM.Kg -1 ). This PEG-Gd 2 o 3 Nanoparticles showed slight contrast enhancement in the glioma region compared to before contrast agent injection, suggesting that PEGylation helps Gd 2 o 3 Nanoparticles accumulated in the glioma area, possibly due to long circulation time and EPR effect. For FA-PEG-Gd 2 o 3 , a clear contrast enhancement was observed in the glioma area even 24 h after injection. In addition, the margins of gl...

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Abstract

The invention relates to a gadolinium oxide targeted magnetic resonance contrast agent, which is polyethylene glycolized Gd2O3 modified by folic acid, expressed as FA-PEG-Gd2O3 and shaped like near-spheres under a transmission electron microscope. A preparation method comprises the following steps: preparing gadolinium oxide nano-particles coated by oleic acid through a high-temperature reduction method, treating gadolinium acetylacetonate in an organic phase to ensure homogeneity and high crystallinity, and performing ligand exchange with silane carboxylic acid to obtain the gadolinium oxide nano-particles with high water solubility. Then, a large number of carboxyl groups of silane are further coupled with NH2-PEG-COOH and NH2-PEG-FA to obtain the gadolinium oxide targeted magnetic resonance contrast agent which is used for early diagnosis of brain glioma.

Description

technical field [0001] The invention relates to a gadolinium oxide targeting magnetic resonance contrast agent. [0002] The present invention also relates to a preparation method of the above-mentioned gadolinium oxide targeting magnetic resonance contrast agent. [0003] The present invention also relates to the application of the above-mentioned gadolinium oxide targeting magnetic resonance contrast agent in the early diagnosis of brain glioma. Background technique [0004] Glioma is a major disease of the human brain and the most common primary tumor of the central nervous system. The treatment method is mainly combined therapy, but the prognosis is extremely poor and the survival rate is low. This is because the early diagnosis and boundary definition of tiny lesions has always been a worldwide problem. Glioma has invasive growth, the boundary between the tumor body and the surrounding normal tissue is not clear, and the contrast agent is difficult to pass through the ...

Claims

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Application Information

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IPC IPC(8): A61K49/12A61K49/10A61K49/18
Inventor 徐群渊叶玲王昊李帅肖宁
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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