Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Synthesis method and application of Fe (II)-based specific MRI contrast agent

A synthesis method and contrast agent technology, applied in chemical instruments and methods, analysis by nuclear magnetic resonance, instruments, etc., can solve the problems of indistinguishability and inaccurate acquisition of iron removal therapy information

Pending Publication Date: 2022-03-15
ZHONGNAN HOSPITAL OF WUHAN UNIV
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Due to the inability of the existing imaging methods to distinguish Fe(II) / Fe(III), it is impossible to accurately obtain information on the efficacy of iron removal therapy. Accurate quantitative analysis of the content and temporal and spatial distribution of Fe(II) in the edema area around the ICH hematoma is of great importance for guidance. It is of great significance to formulate the treatment plan and study the mechanism of Fe(Ⅱ)-mediated nerve injury
In order to obtain the concentration of iron ions in the brain, the researchers found that the sequences that can be used for total iron imaging include T2*WI, SWI, R2*, QSM and other techniques, among which T2*WI and QSM can transfer paramagnetic substances (such as iron, ferritin and Hemosiderin) can be distinguished from diamagnetic substances (such as calcium, water, or myelin) to achieve total iron quantification. However, no matter which of the above imaging methods can only achieve total iron imaging, it is still unable to distinguish Fe(II) and Fe(III), leading to accurate quantification of Fe(II) concentrations in perihematomal edema remains a great challenge

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Synthesis method and application of Fe (II)-based specific MRI contrast agent
  • Synthesis method and application of Fe (II)-based specific MRI contrast agent
  • Synthesis method and application of Fe (II)-based specific MRI contrast agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Embodiment 1: The synthesis method and application thereof based on Fe(II) specific MRI contrast agent provided in this embodiment, specifically include the following steps:

[0029] 1. Synthesis of the first compound: at room temperature, 30mL of DMF containing 6mmol tBut-DOTAGA was added dropwise with 6.2mmol of DIPEA solution, and after 30min, 5mL of HATU (2-(7-azabenzotributazone) dissolved in 6.5mmol was added dropwise azole)-N,N,N',N'-tetramethyluronium hexafluorophosphate) DMF solution; after stirring for 30min, add 6mmol of 5-hydroxyl-2-adamantanone, after stirring for 16 hours, concentrate the resulting solution to dryness and with CH 2 Cl 2 and saturated Na 2 CO 3 aqueous solution extraction, after separation, the organic phase was washed again with saturated aqueous solution, followed by Na 2 CO 3 Washed with brine, washed with Na 2 SO 4 After drying, the first compound is obtained by separation through a chromatographic column.

[0030] 2. Synthesis ...

Embodiment 2

[0034] Embodiment 2: The synthesis method and application thereof based on Fe(II) specific MRI contrast agent provided in this embodiment are basically the same as in Example 1, except that:

[0035] 1. During the synthesis of the first compound: 25 mL of DMF containing 5 mmol tBut-DOTAGA was added dropwise with 5.2 mmol of DIPEA solution, and after 25 min, 3 mL of HATU (2-(7-azabenzotriazepine) dissolved with 6.2 mmol was added dropwise. azole)-N,N,N',N'-tetramethyluronium hexafluorophosphate) DMF solution; after stirring for 35min, add 5mmol of 5-hydroxy-2-adamantanone, and stir for 18 hours.

[0036] 2. During the synthesis of the second compound: 5 mmol of the first compound was dissolved in 10 mL of methanol solution, and 10 mmol of pyridine solution and 6 mmol of methoxyammonium hydrochloride were added dropwise; heated to 80°C in an oil bath and kept for 5 hours.

[0037] 3. During the synthesis of the third compound Fer-DOTA: 4mmol carbon tetrachloride solution of the ...

Embodiment 3

[0039] Embodiment 3: The synthesis method and application thereof based on Fe(II) specific MRI contrast agent provided in this embodiment are basically the same as in Example 1, except that:

[0040] 1. During the synthesis of the first compound: 35 mL of DMF containing 6.8 mmol tBut-DOTAGA was added dropwise with 7 mmol of DIPEA solution, and after 35 min, 7 mL of HATU (2-(7-azabenzotriazole) dissolved with 7 mmol was added dropwise. )-N,N,N',N'-tetramethylurea hexafluorophosphate) DMF solution; after stirring for 35min, add 6mmol of 5-hydroxyl-2-adamantanone, and stir for 18 hours.

[0041] 2. During the synthesis of the second compound: 5.5 mmol of the first compound was dissolved in 25 mL of methanol solution, and 13 mmol of pyridine solution and 6.8 mmol of methoxyammonium hydrochloride were added dropwise; heated to 100°C in an oil bath and kept for 5 hours.

[0042] 3. During the synthesis of the third compound Fer-DOTA: 3mmol carbon tetrachloride solution of the second...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a synthesis method and application of a Fe (II)-based specific MRI contrast agent, and the synthesis method comprises the following steps: carrying out a reaction on tBut-DOTAGA, N, N-diisopropylethylamine DIPEA, 2-(7-azabenzotriazole)-N, N, N ', N'-tetramethylurea hexafluorophosphate HATU and 5-hydroxy-2-adamantanone to synthesize a first compound; performing reaction synthesis on the first compound, a pyridine solution and methoxy ammonia hydrochloride to obtain a second compound; introducing ozone gas into the second compound under an anaerobic condition, and carrying out column separation to obtain a third compound Fer-DOTA; and stirring the third compound and trifluoroacetic acid (TFA) for reaction, adjusting the pH value, adding gadolinium chloride GdCl3 for stirring reaction, and performing high performance liquid chromatography separation to obtain the Fe (II)-based specific MRI contrast agent. Gd-DOTA is covalently bound to a Fe (II) selective group through a chemical bond, so that the Gd-DOTA has Fe (II) selective enrichment capacity, Fe (II) responsive enrichment of Gd-DOTA is realized, and the contrast agent concentration and T1WI signal intensity of a Fe (II)-rich tissue are improved in a targeted manner, so that spatial and temporal distribution of Fe (II) in an ICH edema region is established, and quantitative MRI imaging of Fe (II) is realized.

Description

technical field [0001] The invention relates to the technical field of molecular imaging, in particular to a synthesis method based on Fe(II) specific MRI contrast agent and its application. Background technique [0002] Intracerebral Hemorrhage (ICH) usually refers to non-traumatic cerebral parenchymal hemorrhage, which accounts for about 24% of all strokes and has high mortality and morbidity. After cerebral hemorrhage, a large amount of Fe(II) released by the degradation of hemoglobin (Hb) gradually accumulates in the edema area around the hematoma, and the excess Fe(II) destroys the blood-brain barrier through peroxidation, and causes iron-dependent related cell death and Nerve damage. At present, studies have found that treatment with deferoxamine (iron chelator) can reduce brain edema, neuron death, brain atrophy and neurological deficits in rats and pigs, and quantify Fe in perihematoma edema by non-invasive imaging methods such as MRI. The concentration of (Ⅱ) help...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D257/02C09K11/06G01N24/08
CPCC07D257/02C09K11/06G01N24/087C09K2211/182
Inventor 吴波邓凯李忆张才菊金什琦徐海波
Owner ZHONGNAN HOSPITAL OF WUHAN UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products