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Preparation method of SPECT/CT (Single Photon Emission Computed Tomography/Computed Tomography) dual-mode imaging contrast agent based on second-generation polyamide-amine dendritic polymer

An amine dendritic macromolecule, dual-mode imaging technology, applied in general/multifunctional contrast agents, preparation of X-ray contrast agents, preparations for in vivo tests, etc., can solve the problems of undiscovered preparation and application, and achieve Good SPECT/CT imaging effect, mild reaction conditions, and improved biocompatibility

Inactive Publication Date: 2017-10-24
DONGHUA UNIV +1
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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 SPECT / CT dual-modal 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. and chelated radionuclides 99m Report on preparation and application of Tc SPECT / CT dual-modality imaging contrast agent

Method used

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  • Preparation method of SPECT/CT (Single Photon Emission Computed Tomography/Computed Tomography) dual-mode imaging contrast agent based on second-generation polyamide-amine dendritic polymer
  • Preparation method of SPECT/CT (Single Photon Emission Computed Tomography/Computed Tomography) dual-mode imaging contrast agent based on second-generation polyamide-amine dendritic polymer
  • Preparation method of SPECT/CT (Single Photon Emission Computed Tomography/Computed Tomography) dual-mode imaging contrast agent based on second-generation polyamide-amine dendritic polymer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] (1) 20.0 mg of the second generation polyamidoamine dendrimers (G2.NH 2 ) was dissolved in 3.0mL DMSO, and 3.0mL radionuclide was added dropwise 99m The dimethyl sulfoxide solution (5.5 mg / mL) of the Tc chelating agent NOTA was stirred and reacted at room temperature for 24 hours, and the dialysis bag with a molecular weight cut-off of 1000 was used for dialysis for 3 days (2 L of distilled water was used for each dialysis, and the water was changed 9 times) ), and G2-NOTA was obtained after freeze-drying. 1 The H NMR test results show that the chemical shift peaks at 2.3-3.2ppm and 3.3-3.4ppm in the spectrum correspond to G2.NH respectively 2 and NOTA characteristic peaks. Calculated from the integral area, each G2.NH 2 The surface is modified with about 3.1 NOTA ( figure 1 a).

[0040] (2) Mix 26.9mg polypeptide RGD and 65mg COOH-PEG-MAL in DMSO solution, stir and react for 24 hours to obtain COOH-PEG-MAL, and dialyze with a dialysis bag with a molecular weight ...

Embodiment 2

[0045] Material Stability Test Results

[0046] Take the aqueous solution (0.4 mg / mL) of the product obtained in (4) in Example 1, place it at different temperatures for 0.5 hours, measure its ultraviolet spectrum, and determine the stability of the product at different temperatures. In addition, the aqueous solution (0.4mg / mL) of the product obtained in (4) in Example 1 is prepared into a solution with a pH of 5-8 with acetic acid-sodium acetate buffer solution and PBS buffer solution respectively, and its ultraviolet spectrum is measured to determine that the product is in Stability at different pH. The results show that: in image 3 It can be seen that the G2-NOTA-PEG-RGD@Au( image 3 a and 3c) and the control material G2-NOTA-mPEG@Au ( image 3 b and 3d) Nanoparticles have a characteristic absorption peak at 500-550nm, and within a certain temperature (4°C-60°C) and pH (5-8) range, the absorption peak does not shift significantly, which shows that the present invention ...

Embodiment 3

[0048] Get the product obtained in (4) in Example 1 and use distilled water as a solvent to prepare a mother solution with a gold concentration of 0.04M. Afterwards, 0.02, 0.01 and 0.005M samples were serially diluted. At the same time, taking iohexol for clinical use as the control material and adding distilled water to dilute samples with corresponding iodine concentrations, and CT imaging tests were performed on the two groups of materials respectively. The test results show that the G2-NOTA-PEG-RGD@Au particles prepared in the present invention have better CT imaging effects than the traditional contrast agent iohexol ( Figure 5 a) and X-ray attenuation coefficient ( Figure 5 b), indicating that it has good potential CT imaging capabilities.

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Abstract

The invention relates to a preparation method of SPECT / CT (Single Photon Emission Computed Tomography / Computed Tomography) dual-mode imaging contrast agent based on a second-generation polyamide-amine dendritic polymer. The method comprises the following steps: by taking the second-generation polyamide-amine dendritic polymer as a template material, sequentially modifying a radionuclide 99mTc chelating agent NOTA and a pegylated RGD (Arginine-Glycin-Aspartate) molecule on the surface; coating gold nanoparticles through an in-situ reduction synthesis method; and finally, labeling the radionuclide 99mTc, thereby obtaining the product. The SPECT / CT contrast agent prepared by the method disclosed by the invention has excellent colloidal stability, excellent biocompatibility, long blood circulation time and excellent in-vitro / vitro SPECT / CT imaging effect, has a specific targeting effect on C6 cells of an alphavbeta3 integrin receptor on the cell membrane surface and provides a good thought for developing a novel dual-mode nano contrast agent.

Description

technical field [0001] The invention belongs to the field of contrast agents, in particular to a method for preparing a SPECT / CT dual-mode imaging contrast agent based on second-generation polyamide-amine dendrimers. Background technique [0002] In nuclear medicine imaging, SPECT or PET imaging equipment can receive the rays emitted by radionuclides, and can clearly observe the functional signals of contrast agents participating in various physiological, biochemical and metabolic aspects in the living body, and obtain qualitative, quantitative and localized clinical disease diagnosis and treatment result. Compared with traditional morphological imaging methods (CT, B-ultrasound, MRI), this imaging method can reflect the changes in blood flow, receptor density and activity, metabolism and function of organs or tissues, and has become a clinical tool for diagnosis and treatment of diseases. one of the most advanced technologies. At the same time, nuclear medicine imaging al...

Claims

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Application Information

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IPC IPC(8): A61K51/06A61K51/08A61K51/04A61K51/02A61K49/04A61K49/00A61K103/10
CPCA61K51/065A61K49/0002A61K49/04A61K51/02A61K51/0482A61K51/082
Inventor 沈明武许晓迎李鑫王鹏史向阳赵凌舟赵晋华
Owner DONGHUA UNIV
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