Preparation method of G2.NH2 based manganese-based MR/CT (Magnetic Resonance/Computerized Tomography) dual-mode imaging contrast agent with RGD (arginine-glycine-aspartic acid) targeting function

A dual-modal imaging, G2-NOTA technology, applied in general/multifunctional contrast agents, preparation of X-ray contrast agents, preparations for in vivo experiments, etc., can solve the problem of no discovery, and achieve good specific targeting effect, good MR/CT imaging effect, and the effect of improving biocompatibility

Inactive Publication Date: 2018-09-21
DONGHUA UNIV +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] A search of domestic and foreign literature and patents on MR / CT dual-modality contrast agents shows that: so far, no second-generation polyamide-amine dendrimers modified with the chelating agent NOTA and polypeptide RGD have been found to wrap gold nanoparticles. Preparation of MR / CT dual-modal imaging contrast agent with chelated divalent manganese ions and its application in in situ glioma imaging

Method used

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  • Preparation method of G2.NH2 based manganese-based MR/CT (Magnetic Resonance/Computerized Tomography) dual-mode imaging contrast agent with RGD (arginine-glycine-aspartic acid) targeting function
  • Preparation method of G2.NH2 based manganese-based MR/CT (Magnetic Resonance/Computerized Tomography) dual-mode imaging contrast agent with RGD (arginine-glycine-aspartic acid) targeting function
  • Preparation method of G2.NH2 based manganese-based MR/CT (Magnetic Resonance/Computerized Tomography) dual-mode imaging contrast agent with RGD (arginine-glycine-aspartic acid) targeting function

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] (1) Take 30.0mg G2.NH 2 and 30.4mg NOTA were respectively dispersed in 5mL and 4mL DMSO, after complete dissolution, mixed and stirred at room temperature for 24h to obtain a mixed solution of product G2-NOTA, and then dialyzed for 3 days with a dialysis bag with a molecular weight cut-off of 1000 (each dialysis The distilled water used was 2L, and the water was changed 9 times), vacuum freeze-dried to obtain G2-NOTA; wherein G2.NH 2 The molar ratio to NOTA is 1:5.

[0042] (2) Dissolve 75.0mg COOH-PEG-MAL and 25.0mg RGD in 6mL and 3mL DMSO respectively. After complete dissolution, mix and stir at room temperature for 74 hours. After the reaction, dialyze 3 days (2 L of distilled water for each dialysis, a total of 9 water changes), vacuum freeze-drying to obtain RGD-PEG-COOH; wherein the molar ratio of COOH-PEG-MAL and RGD is 1:1.2.

[0043] (3) Dissolve 90 mg of COOH-PEG-RGD obtained in step (2) in 15 mL of DMSO, add 5 mL of EDC in DMSO (15.5 mg / mL) for activation f...

Embodiment 2

[0052] The present invention uses proton nuclear magnetic resonance spectrum ( 1 H NMR), ultraviolet-visible absorption spectroscopy (UV-Vis), high-resolution transmission electron microscopy (TEM), inductively coupled plasma optical emission spectroscopy (ICP-OES) and other methods to characterize the physical and chemical properties of materials.

[0053] 1 H NMR test:

[0054] Carry out to the G2-NOTA that makes in embodiment 1 1 H NMR test, the spectrum is as figure 1 As shown in (a), the chemical shift peaks at 2.3-3.2ppm and 3.3-3.4ppm correspond to G2.NH respectively 2 and NOTA characteristic peaks. Calculated from the integral area, each G2.NH 2 The surface is modified by about 3.6 NOTA.

[0055] Carry out to the RGD-PEG-COOH that makes in embodiment 1 1 H NMR test, the spectrum is as figure 1 As shown in (b), the chemical shift peaks appearing at 3.4-3.6ppm and 7.1-7.3ppm correspond to the characteristic peaks of polyethylene glycol and RGD, respectively. A...

Embodiment 3

[0066] The present invention evaluates the cytocompatibility of materials by Cell Counting Kit-8 (CCK-8) method and fluorescent inverted microscope, and finally utilizes in vivo MR / CT imaging to characterize the prepared low-algebra dendrimer with dual-mode imaging function. Molecular diagnostic efficacy in orthotopic glioma models.

[0067] Take the targeted G2-NOTA(Mn)-PEG-RGD@Au material prepared in Example 1 and the non-targeted G2-NOTA(Mn)-mPEG@Au material prepared in Comparative Example 1, using distilled water as a solvent, To prepare aqueous solutions of nanoparticles with Mn concentrations of 0.1, 0.2, 0.4, 0.8 and 1.6 mM, use T 1 The magnetic resonance imager measures the T of the two materials 1 Relaxation time and scan MR imaging pictures. The scanning parameters are: repetition time (TR)=4000ms, echo time (TE)=60ms, thickness=0.6mm, resolution=156mm×156mm. Test results such as Figure 4 Shown: the reciprocal of the relaxation time of the G2-NOTA(Mn)-PEG-RGD@Au...

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Abstract

The invention relates to a preparation method of a G2.NH2 based manganese-based MR / CT (Magnetic Resonance / Computerized Tomography) dual-mode imaging contrast agent with an RGD (arginine-glycine-aspartic acid) targeting function. The preparation method comprises the following steps: mixing G2.NH2 and NOTA and reacting to obtain G2-NOTA; then mixing COOH-PEG-MAL and RGD and reacting to obtain COOH-PEG-RGD; after carrying out activation treatment, reacting with the G2-NOTA to obtain G2-NOTA-PEG-RGD; reacting with a chloroauric acid solution and a pre-cooled sodium borohydride solution to obtain G2-NOTA-PEG-RGD@Au; mixing G2-NOTA-PEG-RGD@Au with MnSO4 and reacting to obtain a product. The MR / CT contrast agent prepared by the preparation method has good colloid stability, excellent biocompatibility, relatively long blood circulation time and relatively high relaxation rate; the MR / CT contrast agent has a specific targeting effect on in-situ brain glioma of a mouse and a good thought is provided for developing a novel dual-mode nano contrast agent.

Description

technical field [0001] The invention belongs to the technical field of contrast agents, in particular to a G2.NH-based 2 Preparation method of manganese-based MR / CT dual-modality imaging contrast agent. Background technique [0002] In recent years, cancer has become a major threat to human life and health. Statistics show that in China, which accounts for one-fifth of the world's population, about 22% of new cancer cases and 27% of cancer deaths occur every year, and there are almost 6 cancer deaths per minute on average. Humans are diagnosed with malignant tumors, so finding methods for accurate diagnosis and effective treatment of cancer is a subject that scientists have been working on. As an emerging discipline that has been booming in recent years, molecular imaging can effectively obtain information about living tissues at the molecular and cellular levels by detecting the physiological and pathological changes of the body and then processing the images. The develop...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/14A61K49/04
CPCA61K49/0002A61K49/04A61K49/14
Inventor 沈明武许晓迎王鹏张昌昌史梦晗史向阳王玥夏进东
Owner DONGHUA UNIV
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