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

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...

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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

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