Antibody labeled porphyrin iso-indole free radical compound and synthetic method thereof

A porphyrin isonitrogen and antibody labeling technology, applied in the fields of medicine and chemistry, can solve the problems of no tissue or organ selectivity or targeting, the influence of animal physiology and pathological processes, and fast metabolism, and achieve a small dosage. , low cost, long imaging time

Inactive Publication Date: 2015-05-20
WUHAN INSTITUTE OF TECHNOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] In the current EPRI diagnosis, the concentration of electron paramagnetic resonance imaging diagnostic agent introduced into the body must be greater than 0.1mmol / kg to obtain effective imaging signals, and high concentrations of stable free radicals often affect and interfere with the physiological and pathological processes of animals
Commonly used nitroxide radicals, such as 4-carboxylate-TEMPO (2,2,6,6-tetrmethyl-1-piperidinoxy) and 5-carboxylate-isozaindene nitroxide radical (CTMIO) are small molecules The stable free radicals have fast metabolism in the body, short retention time, low utilization rate, no tissue or organ selectivity or targeting, especially poor imaging effect on tumors

Method used

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  • Antibody labeled porphyrin iso-indole free radical compound and synthetic method thereof
  • Antibody labeled porphyrin iso-indole free radical compound and synthetic method thereof
  • Antibody labeled porphyrin iso-indole free radical compound and synthetic method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] 0.0476mg m-maleimide benzoyl-N-N-hydroxysuccinimide ester (1.515×10 -4 mmol, MBS, MW314.25) was added to 0.143 mg 5-(1',1',3',3'-tetramethyl-isozaindene-2'-nitrogen oxide radical)-15-aminophenyl -10,20-bis(sodium sulfonate phenyl)porphyrin (1.515×10 -4 mmol, MW947) was dissolved in 1 mL of phosphate buffer (0.01 mol / L, pH7.4), and vortexed at room temperature for 4 hours. Add 1 mg GPC3 antibody (66kDa, 1.515×10-5mmol) and vortex shake at room temperature for 4 hours. The reaction solution was dialyzed against ultra-pure water for 12 hours to obtain an antibody-labeled porphyrin isoazepine radical compound solution.

[0040] X-band EPR spectrum: The antibody-labeled porphyrin isoazepine free radical compound of Example 1 was dissolved in twice distilled water to form a dilute solution, and its electron paramagnetic resonance performance was measured on a Brucker EPR A300 electron paramagnetic resonance instrument. attached figure 1 It can be seen that the antibody-la...

Embodiment 2

[0042]0.0514mg N[ε-maleimidocaproic acid]hydrazide trifluoroacetic acid (1.515×10-4mmol, EMCH, MW339.27) and 0.029mg 1-ethyl-3-[3-dimethylaminopropyl Base] carbodiimide hydrochloride (1.515×10-4mmol, EDC, MW191.70) was added to 0.15mg of 5,10-bis(1',1',3',3'-tetramethyl-isozaindene -2'-nitrogen oxide radical)-15,20-bis(p-acetoxy)porphyrin (1.515×10-4mmol, MW990) dissolved in 1mL of acetate buffer (0.01mol / L,pH4.5) vortexed at room temperature for 4 hours. The solvent was evaporated to dryness under reduced pressure, and 1 mg of GPC3 antibody (66 kDa, 1.515×10-5 mmol) was added to the solid in 1 mL of phosphate buffer (0.01 mol / L, pH 7.4), and vortexed at room temperature for 4 hours. The reaction solution was dialyzed against ultra-pure water for 12 hours to obtain an antibody-labeled porphyrin isoazepine radical compound solution.

Embodiment 3

[0044] 0.029mg 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (1.515×10-4mmol, EDC, MW191.70) was added to 0.172mg 5-(1',1',3 ',3'-Tetramethyl-isozaindene-2'-nitrogen oxide radical)-10,15-bis(p-iodomethanepyridyl)-20-(p-butanoylpyridyl)-porphyrin (1.515×10-4mmol, MW1138) was dissolved in 1mL of acetate buffer (0.01mol / L, pH4.5), and vortexed at room temperature for 4 hours. The solvent was evaporated to dryness under reduced pressure, and 1 mg of GPC3 antibody (66 kDa, 1.515×10-5 mmol) was added to the solid in 1 mL of phosphate buffer (0.01 mol / L, pH 7.4), and vortexed at room temperature for 4 hours. The reaction solution was dialyzed against phosphate buffer for 12 hours to obtain an antibody-labeled porphyrinindene free radical compound solution.

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Abstract

The invention particularly relates to a kind of antibody labeled porphyrin iso-indole free radical compound, which has the structural formula as shown in the formula I, and further relates to a synthetic method of the antibody labeled porphyrin iso-indole free radical compound and the application of the antibody labeled porphyrin iso-indole free radical compound used as an electron paramagnetic resonance diagnostic agent. A porphyrin iso-indole free radical compound and a tumor-targeting group GPC3-mAb monoclonal antibody are connected through a covalent bond so as to form a compound; the compound forms the electron paramagnetic resonance diagnostic agent with a medicinal vector or a forming body. The diagnostic agent can be selectively absorbed by hepatoma cells, the targeted imaging can be achieved, the contrast degree and definition of imaging can be improved, the imaging effect is good, the using amount is low, and the toxicity is less.

Description

technical field [0001] The invention relates to the fields of medicine and chemistry, in particular to a class of antibody-labeled porphyrin isoazepine free radical compounds, as well as its synthesis method and application as a diagnostic agent. Background technique [0002] Electron Paramagnetic Resonance [Electron Paramagnetic (Spin) Resonance, EPR or ESR] is the most effective means to detect and analyze biological free radicals. In recent years, electron paramagnetic resonance imaging (EPR Imaging, EPRI), as a method for in vivo detection and multidimensional imaging analysis of active paramagnetic substances such as free radicals, is now widely used in various tissues or organs of experimental animals, such as Imaging detection of tumor, heart, brain, liver, kidney, stomach, etc. [0003] Compared with magnetic resonance imaging (MRI) and X-ray CT, EPRI has the following advantages for cancer detection under the enhancement of EPR Imaging Contrast Agent: [0004] 1) ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K16/30
Inventor 鄢国平鄢珈睿陈群二
Owner WUHAN INSTITUTE OF TECHNOLOGY
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