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Functionalized dendrimer-based SPECT-CT bimodal imaging contrast agent and preparation method thereof

A dendrimer, dual-mode imaging technology, applied in the preparation of X-ray contrast agents, radioactive carriers, etc., can solve the problems of preparation and application of SPECT/CT contrast agents that have not been found

Inactive Publication Date: 2014-11-26
DONGHUA UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] A search of domestic and foreign literature and patents on SPECT / CT dual-modality contrast agents shows that: at present, no chelated gold nanoparticles based on dendrimers have been found. 99m Report on preparation and application of Tc SPECT / CT contrast agent

Method used

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  • Functionalized dendrimer-based SPECT-CT bimodal imaging contrast agent and preparation method thereof
  • Functionalized dendrimer-based SPECT-CT bimodal imaging contrast agent and preparation method thereof
  • Functionalized dendrimer-based SPECT-CT bimodal imaging contrast agent and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] Such as figure 1 shown, preparation 99m Tc-Au-Ac DENPs.

[0065] (1) 20.0mg of the fifth generation polyamidoamine dendrimers (G5.NH 2 , purchased from Dendritech Company) was dissolved in 15 mL of water, and 2 mL of an aqueous solution (1.1 mg / mL) of diethylenetriaminepentaacetic acid cyclic anhydride (cDTPAA, purchased from Sigma Aldrich) was added dropwise, and the reaction was stirred at room temperature for 8 h to obtain G5- DTPA; at the same time, add 5 mL of 1-ethyl-(3-dimethylaminopropyl) carbodiimide (EDC, purchased from Sigma Aldrich) in 10 mL of mPEG-COOH in water (7.69 mg / mL) in water (7.69 mg / mL) and stirred for 2h, then the mPEG-COOH (purchased from Shanghai Yanyi Biotechnology Co., Ltd.) activated by EDC was added to the G5-DTPA solution, stirred for 1-3d, and the functionalized dendrimer (G5 -DTPA-mPEG) solution;

[0066] (2) Add 2.1mL chloroauric acid solution (30mg / mL) to the G5-DTPA-mPEG solution obtained in (1) and stir for 30min, the solution t...

Embodiment 2

[0070] Such as figure 1 shown, preparation 99m Tc-Au-Gly DENPs.

[0071] (1) 20.0mg G5.NH 2 Dissolve in 15mL water, and add 2mL cDTPAA aqueous solution (1.1mg / mL) dropwise, stir the reaction at room temperature for 8h to obtain G5-DTPA; at the same time, add 5mL EDC to 10mL mPEG-COOH aqueous solution (7.69mg / mL) Aqueous solution (7.69mg / mL) and stirred for 2h, then mPEG-COOH activated by EDC was added to the G5-DTPA solution, and stirred for 1-3d to obtain a functionalized dendrimer (G5-DTPA-mPEG) solution;

[0072] (2) Add 2.1mL chloroauric acid solution (30mg / mL) to the G5-DTPA-mPEG solution obtained in (1) and stir for 30min, the solution turns light yellow, then add 2.8mL sodium borohydride aqueous solution (10mg / mL ), the solution instantly turns dark red, and the reaction is stirred for 1-4h. Then 84 μL glycidol was added and the reaction was stirred for 24 h. Finally, the reaction product was dialyzed in phosphate buffer solution 2L×3 and distilled water 2L×3 suc...

Embodiment 3

[0076] MTT assay was used to study the cytotoxicity of the prepared Au-Ac DENPs and Au-Gly DENPs.

[0077] Collect the logarithmic phase human ovarian cancer cell line (SK-OV-3 cells), add it to a 96-well cell culture plate, add 200 μL of cell-containing RPMI1640 medium to each well to make the cell density to 8000 / well; then place in a cell culture incubator (5%CO 2 , 37°C) for 24 hours, discard the medium and add 180 μL of fresh medium, and then add 20 μL of PBS buffer containing different concentrations of Au-Ac DENPs and Au-Gly DENPs (the final gold concentrations were 0, 2.5, 5, 10, 20, 40, 80 μM) to verify the effect of the material on the growth of SK-OV-3 cells. All test groups were set with 5 wells as a parallel group; after incubation in the incubator for 24 hours, 20 μL of MTT solution (5 mg / mL) was added to each well, and after 4 hours of incubation, the culture solution in the wells was carefully sucked, and the Add 200 μL of DMSO, shake on a shaker in the dark ...

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Abstract

The invention relates to a functionalized dendrimer-based SPECT-CT bimodal imaging contrast agent and a preparation method thereof. The functionalized dendrimer-based SPECT-CT bimodal imaging contrast agent is obtained by pegylation modified fifth polyamide-amine dendrimer as a polymer carrier material; connecting diethylenetriaminepentaacetic acid on the dendrimer surface through covalent grafting; coating gold nanoparticles through an in-situ synthesis method; carrying out acetylation or hydroxylation on residual surface amino groups; and marking <99m>Tc. The functionalized dendrimer-based SPECT-CT bimodal imaging contrast agent has a very good SPECT / CT imaging effect, realizes SPECT / CT imaging of different in-vivo tissue sites of a mouse, lays good foundation for development of multi-functional tissue specific contrast agent, and has wide application prospects.

Description

technical field [0001] The invention belongs to the field of contrast agents, in particular to a functional dendrimer-based SPECT-CT dual-mode imaging contrast agent and a preparation method thereof. Background technique [0002] Nuclear medicine imaging uses radionuclide-labeled chemical substances as imaging agents or radiopharmaceuticals to be introduced into living organisms to display the physiological and biochemical processes in the body. By receiving the radiation emitted by radionuclides by nuclear medicine SPECT or PET imaging equipment, it is possible to clearly observe the functional information of the contrast agent participating in various physiological, biochemical and even metabolic aspects of the organism, and obtain qualitative, quantitative and localized clinical disease diagnosis and treatment results. The most prominent advantage of radionuclide imaging in nuclear medicine is its functional imaging. Due to its unique functional imaging characteristics, c...

Claims

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Application Information

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IPC IPC(8): A61K51/06A61K49/04A61K103/10
Inventor 史向阳温诗辉赵晋华赵凌舟
Owner DONGHUA UNIV
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