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A kind of compound, preparation method and MRI imaging application thereof

A compound and complexation technology, applied in the field of medical detection, can solve problems such as strong immunogenicity, recognition, phagocytosis and degradation, and narrow application range

Active Publication Date: 2021-06-15
THE FIRST AFFILIATED HOSPITAL OF HAINAN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the molecular weight of the antibody connected to the MRI contrast agent is usually relatively large, with strong immunogenicity, and is easily recognized, phagocytized and degraded by the human immune system, which greatly reduces the targeting of positive MRI contrast agents. Therefore, MRI targeted contrast agents are basically are still in the laboratory stage
In addition, different tumor cell membranes express different specific proteins, so the antibody carried by the positive MRI contrast agent can only be used for the diagnosis of one tumor, and its application range is relatively narrow

Method used

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  • A kind of compound, preparation method and MRI imaging application thereof
  • A kind of compound, preparation method and MRI imaging application thereof
  • A kind of compound, preparation method and MRI imaging application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Embodiment 1: Preparation of MRI contrast agent of the present invention

[0051] ①Thaw the experimental group A: 1.1g VEGF small peptide (0.187mmol) resin, control group B: 1g random small peptide (0.14mmol) resin;

[0052] ② Add VEGF small peptide resin to centrifuge tube A, add random small peptide resin to centrifuge tube B, then add DOTA-tris (0.5mmol, 290mg), HBTU (1mol, 379mg), HOBT (100mg), DMF 15ml , shaker 350 rpm, reaction 60 minutes;

[0053] ③Introduce the mixture in the centrifuge tubes A and B into the solid-phase synthesis tubes A and B, add 500 μl of DIPEA to each tube, shake at 350 rpm, and react for 2 hours;

[0054] ④ Suction filter A and B solid phase synthesizers respectively, add TFA96.5%, triisobutyl silicone 1.0%, water 2.5%, shaker at 350 rpm, and react for 5 hours;

[0055] ⑤ Diethyl ether precipitation Collect the reactants in the solid-phase synthesizer A and B, centrifuge 3 times at 4000 rpm, collect the precipitate, put it in a desiccato...

Embodiment 2

[0058] Embodiment 2: Mass Spectrometry and T1 Relaxation Rate Detection of MRI Contrast Agents of the Present Invention

[0059] According to "MR molecular imaging of prostate cancer with a peptide-targeted contrast agent in a mouse orthotopic prostate cancer model" (PharmRes.2012Apr; 29(4):953-60), the MRI contrast agent prepared in Example 1 was detected by mass spectrometry, see results figure 2 .

[0060] figure 2 It shows that the molecular weight of the MRI contrast agent prepared in Example 1 is 2133.795, which is consistent with the theoretical molecular weight, which proves that the coupling is successful and the synthesis is correct.

[0061] Prepared according to "Synthesis and evaluation of a polydisulfide with Gd-DOTAmonoamide side chains as a biodegradable macromolecular contrast agent for MRblood pool imaging. Contrast Media Mol Imaging" (2013May-Jun; 8(3):220-8) The predicted rate of the MRI contrast agent, the results are shown in image 3 .

[0062] ...

Embodiment 3

[0063] Embodiment 3: the in vitro targeting cell test of the MRI contrast agent of the present invention

[0064]Tumor cells were divided into experimental group and control group. When the cell growth reached 85% of the bottom area of ​​the bottle, 0-250 μL (0-0.0125 mmol Gd) of VEGF125-136-DOTA-Gd was added to the experimental group, and the same amount of random Small peptide-DOTA-Gd, placed in a 37.5°C incubator for 6 hours, washed 4 times with PBS, 5 minutes each time. Each group was added with 1ml of cell digestion enzyme, digested for 1-2 minutes, sucked into the centrifuge tube, 1.5ml for each tube, added 2% agarose to suspend. 3.0 MRI scan (GE), see the results Figure 4 . Among them, the head coil and T1 scanning parameters are specifically: repetition time / echo time=600 / 15ms, matrix=256×256, layer thickness=2mm, field of view=20cm, signal-to-noise ratio=T1 signal mean value / surrounding noise, region of interest = 2 mm.

[0065] Depend on Figure 4 It can be see...

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Abstract

The invention belongs to the field of medical detection, and specifically relates to a compound, a preparation method and an MRI imaging application thereof. The compound of the present invention is a VEGFR2 targeting small peptide coupled with metal gadolinium DOTA. The VEGFR2 targeting small peptide VEGF125‑136 small peptide in the compound of the present invention can compete for the combination of VEGF165 and VEGFR2, has a small molecular weight, and has no immunogenicity problem in vivo. The compound of the invention is prepared by linking the VEGFR2 targeting small peptide VEGF125-136 with DOTA through an amide bond, and complexing gadolinium into the DOPA ring through a coordination bond, and the preparation method is simple to operate. The compound of the present invention is an MRI positive contrast agent, which has strong targeting to VEGFR2 in vivo and in vitro, can be used as a VEGFR2 target-targeted magnetic resonance imaging contrast agent, and avoids immunogenic defects, and can be applied to various Tumor diagnosis.

Description

technical field [0001] The invention belongs to the field of medical detection, and specifically relates to a compound, a preparation method and an MRI imaging application thereof, in particular to an application as a VEGFR2 target-targeting magnetic resonance imaging contrast agent. Background technique [0002] Magnetic resonance imaging (Magnetic Resonance Imaging, MRI) is a new inspection technology based on the principle that atomic nuclei with magnetic distances can produce transitions between energy levels under the action of a magnetic field. It is realized by radiating energy to the surrounding environment to generate signals. According to the different attenuation of the released energy in different structural environments inside the material, the position and type of the atomic nucleus that constitutes the object can be known by detecting the emitted electromagnetic waves with an external gradient magnetic field. , which can be drawn as a structural image inside t...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/475C07K1/107A61K49/08A61K49/14A61K49/10
Inventor 尤晓光文丽君涂蓉尤涛许一凯
Owner THE FIRST AFFILIATED HOSPITAL OF HAINAN MEDICAL UNIV
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