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Preparation of CT/MRI dual-modality imaging contrast agent based on dendrimer

A dendritic macromolecule, dual-mode imaging technology, applied in the preparation of X-ray contrast agents, preparations for in vivo tests, pharmaceutical formulations, etc., can solve problems such as the preparation and application of CT/MRI contrast agents that have not been found, and achieve Good MR imaging performance, display signal enhancement, good dispersion effect

Inactive Publication Date: 2011-12-28
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] A search of domestic and foreign literature and patents on CT / MRI dual-modality contrast agents shows that: at present, no research has been found on the preparation and application of CT / MRI contrast agents based on dendrimer-coated gold nanoparticles and chelated gadolinium. to report

Method used

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  • Preparation of CT/MRI dual-modality imaging contrast agent based on dendrimer
  • Preparation of CT/MRI dual-modality imaging contrast agent based on dendrimer
  • Preparation of CT/MRI dual-modality imaging contrast agent based on dendrimer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] (1) Dissolve G5PAMAM dendrimer with a dry weight of 22.00 mg in 10 mL of DMSO, and add DOTA-NHS with a dry weight of 6.44 mg dissolved in 4 mL of DMSO solution drop by drop while stirring, wherein DOTA-NHS: dendrimer The molecular molar ratio is 10:1, and the reaction takes 24 hours. Add 2 mL of EDC in DMSO (17.2 mg / mL) to 4 mL of mPEG-COOH in DMSO (8.55 mg / mL), stir for 3 hours and add dropwise to the reaction between G5PAMAM dendrimer and DOTA-NHS solution, stirred for 72 hours.

[0062] (2) Take 10mL of the reaction solution in step (1), add 10mL DMSO and 10mL water, stir and mix well, then add 2.29mL HAuCl 4 Aqueous solution (20mg / mL) was mixed, stirred at room temperature for 30min, the solution turned light yellow, then added 1.236mL of 20mg / mL NaBH 4 Solution (H 2 O:CH 3 OH (volume ratio) = 2:1), the solution turned dark red instantly, and stirred and reacted at room temperature for 3h;

[0063] (3) Add 0.535mL Gd(NO 3 ) 3 ·6H 2 Aqueous solution of O (12 ...

Embodiment 2

[0066] (1) Dissolve G5PAMAM dendrimers with a dry weight of 11.00 mg in 5 mL of DMSO, and add DOTA-NHS with a dry weight of 3.22 mg dissolved in 4 mL of DMSO solution drop by drop while stirring, wherein DOTA-NHS: dendrimer The molar ratio of the macromolecules was 10:1, and the reaction was carried out for 18 hours. In 2 mL of mPEG-COOH in DMSO (8.55 mg / mL), add 1 mL of EDC in DMSO (17.2 mg / mL), stir for 3 hours and then add dropwise to the reaction between G5PAMAM dendrimer and DOTA-NHS solution, stirred for 72 hours.

[0067] (2) Take 6mL of the reaction solution in step (1), add 10mL DMSO and 10mL water, stir and mix well, then add 115mL HAuCl 4 Aqueous solution (20mg / mL) was mixed, stirred at room temperature for 20min, the solution turned light yellow, then added 0.618mL of 20mg / mL NaBH 4 Solution (H 2 O:CH 3 OH (volume ratio) = 2:1), the solution turned dark red instantly, and stirred and reacted at room temperature for 1h;

[0068] (3) Add 0.535mL Gd(NO 3 ) 3 ·6...

Embodiment 3

[0071] Check the two kinds of materials {(Au 0 ) 250 -G5-DOTA (GdIII) 10 -PEG 20 -Ac}DENPs and {(Au 0 ) 250 -G5-DOTA 10 -PEG 20 -CT imaging effect of Ac}DENPs. Take 29.88 mg of the sample of Example 1 and dissolve it in 580 μL of PBS buffer to prepare a solution with a gold concentration of 0.1M, and then dilute it to 200 μL each with a gold concentration of 0.08M, 0.05M, 0.03M, 0.02M, and 0.01M. Take 26.51 mg of the sample of Comparative Example 1 and dissolve it in 580 μL of PBS buffer to prepare a solution with a gold concentration of 0.1M, and then dilute it to 200 μL each with a gold concentration of 0.08M, 0.05M, 0.03M, 0.02M, and 0.01M. The HU value of each sample was tested with a CT tester and the linear relationship between X-ray attenuation and gold concentration was obtained. attached Figure 4 (a) is the CT picture of the sample (where 1 is {(Au 0 ) 250 -G5-DOTA (GdIII) 10 -PEG 20 -Ac}DENPs and 2 are {(Au 0 ) 250 -G5-DOTA 10 -PEG 20 -Ac}DENPs), wi...

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Abstract

The invention relates to a method for preparing a computed tomography (CT) / magnatic resonance imaging (MRI) bimodal imaging contrast agent based on dendrimers. The method comprises the following steps of: (1) adding DOTA-N-hydroxy succinimide (NHS) solution into the fifth generation of poly(amidoamine) (PAMAM) dendrimer solution, adding methoxy poly(ethylene glycol) (mPEG)-COOH solution which is subjected to 1-ethy 1-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC) activation, reacting with stirring, and thus obtaining functionalized dendrimer solution; (2) adding chloroauric acid solution and sodium borohydride solution into the functionalized dendrimer solution, reacting with stirring, adding gadolinium nitrate solution, stirring, adding triethylamine and acetic anhydride, andreacting with stirring for 8 to 24 hours; and (3) dialyzing the solution obtained in the step (2), performing freeze drying treatment, and thus obtaining the contrast agent. The method has a simple preparation process, and experimental conditions are realized at normal temperature and under normal pressure; and the CT / MRI bimodal imaging contrast agent prepared by the method has a good CT / MRI effect, and a favorable foundation is laid for the development of a novel multifunctional contrast agent.

Description

technical field [0001] The invention belongs to the field of preparation of CT / MRI dual-imaging contrast agents, and in particular relates to a preparation method of dendrimer-based CT / MRI dual-mode imaging contrast agents. Background technique [0002] Because CT and MRI imaging have their own advantages and disadvantages in medical imaging, in order to improve the sensitivity and accuracy of early diagnosis of diseases, the two are often combined organically, so that the current imaging examination not only expands the scope of examination, but also improves the diagnostic level. However, when CT and MRI are used as medical imaging detection methods in a complementary form, two imaging contrast agents, CT and MRI, are usually required. Although a variety of CT or MRI imaging contrast agents can achieve better contrast effects, if two contrast agents are used, on the one hand, it will cause inconvenience to clinical application, and on the other hand, it will increase the ...

Claims

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Application Information

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IPC IPC(8): A61K49/12A61K49/04
Inventor 史向阳温诗辉
Owner DONGHUA UNIV
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