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Low-field high-relaxation rate magnetic resonance imaging (MRI) contrast agent and preparation method

A technology of contrast agent and fullerene carboxylic acid, which is applied in the direction of nuclear magnetic resonance/magnetic resonance imaging contrast agent, etc., can solve the problems of poor targeting and low efficiency, and achieve the effect of improving relaxation efficiency and overcoming high technical cost.

Active Publication Date: 2013-03-20
赤峰福纳康生物技术有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, traditional MRI contrast agents still have disadvantages such as low efficiency and poor targeting.

Method used

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  • Low-field high-relaxation rate magnetic resonance imaging (MRI) contrast agent and preparation method
  • Low-field high-relaxation rate magnetic resonance imaging (MRI) contrast agent and preparation method
  • Low-field high-relaxation rate magnetic resonance imaging (MRI) contrast agent and preparation method

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Embodiment 1: Preparation of Gd-DTPA-HSA macromolecular contrast agent

[0039] a) Dissolve 100mg HSA in 5mL PBS (pH 7.4) buffer solution, directly add cDTPA bisanhydride solid (cDTPA:HSA=200:1, molar ratio) in batches, use 0.1M NaOH solution to adjust pH=7, at room temperature Reaction 2h;

[0040] b) Separation and purification of the system obtained after the reaction by Sephadex G-25 (PD-10 mesh) with Sephadex, eluent: 0.5M CH 3 COONa (pH=6.0), was monitored with a UV-Vis spectrophotometer at 280nm to obtain a HSA-DTPA solution;

[0041] c) 112mg GdCl 3 ·6H 2 O(GdCl 3 ·6H 2 (O:HSA=200:1, molar ratio) was dissolved in 1 mL CH 3 COONa (pH=6.0, 0.5M) buffer solution was added to the HSA-DTPA solution, stirred at room temperature for 2 hours, and the small molecules were removed by dialysis using a Mw=12,000-14,000 dialysis bag, and then unreacted was removed by an ultrafiltration centrifuge tube with Mw=10,000 substances, monitored by measuring the conductivity ...

Embodiment 2

[0049] Embodiment 2: Preparation of conjugates of Gd-DTPA-HSA and fullerene carboxylic acid derivatives

[0050] a)(C 60 [C(COOH) 2 ] x (x=3)) Preparation: Reference (Bingel, C., Cyclopropanierung vonFullerenen. Chemische Berichte 1993, 126(8), 1957-1959.) Preparation of fullerene carboxylate derivatives followed by hydrolysis using NaH to give fullerene carboxylic acid derivatives.

[0051] b) 10mg fullerene carboxylic acid derivative (C 60 [C(COOH) 2 ] x (x=3)) was dissolved in 10mL MES (pH 5.5) buffer, added 10mg EDC and 5mg NHS (C 60 [C(COOH) 2 ] x With EDC, NHS molar ratio is 1:6:6), reaction at room temperature for 2h, to obtain fullerene carboxylic acid active ester.

[0052] c) Add 10 mg of Gd-DTPA-HSA to the above-mentioned fullerene carboxylic acid active ester solution, stir overnight at room temperature, use a Mw=12,000-14,000 dialysis bag to remove small molecules, and then use a Mw=10,000 ultrafiltration centrifuge tube Remove unreacted fullerene molecu...

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Abstract

The invention discloses a high-efficiency magnetic resonance imaging (MRI) macromolecular contrast agent applied to low-field MRI and a preparation method and application thereof. The MRI macromolecular contrast agent can be prepared according to the following steps of: a) dissolving a fullerene carboxylic acid derivative in a 2-(N-morpholino) ethanesulfonic acid (MES) buffer solution, adding 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), and reacting at room temperature to obtain a fullerene carboxylic acid active ester solution; and b) adding gadolinium diethylenetriamine pentaacetic acid human serum albumin (Gd-DTPA-HAS) into the fullerene carboxylic acid active ester solution, stirring, reacting, and then obtaining the MRI contrast agent. The relaxation rate of the Gd-DTPA-HAS-fullerene macromolecular contrast agent is obviously improved under the condition of low field of 0.5T, and obvious tissue contrast ratio can be obtained under the condition of reducing the dosage of the contrast agent; and most importantly, the MRI contrast agent can be used as an MRI molecular probe which can be used for exploring body distribution and metabolism behavior of nanometer materials such as functionalized fullerene derivatives.

Description

technical field [0001] The invention relates to a low-field high-relaxation MRI contrast agent, a preparation method and application thereof. Background technique [0002] Magnetic resonance imaging (Magnetic Resonance Imaging, MRI) technology is one of the latest achievements in the development of medical imaging since the 1980s. It is a non-destructive, high-resolution imaging examination method. It can not only provide high-resolution (50μm) three-dimensional images of soft tissue without using harmful rays, but also provide real-time information on the physiology and anatomy of the lesion at the same time. It is one of the most effective methods for diagnosing tumors and guiding surgical operations. 1 [Lauffer R.B., Chem. Rev. [J], 1987, 87(5): p.901-927.]. Although conventional MRI itself has excellent soft tissue contrast, when the diseased tissue has T 1 and T 2 When the value is low, no significant contrast can be produced between normal and diseased tissue. At t...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/06
Inventor 舒春英甄明明王春儒郑俊鹏
Owner 赤峰福纳康生物技术有限公司
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