Radioactive C-MET-targeted affinity micromolecular compound and application thereof

A small molecule compound, radioactive technology, applied in the directions of radioactive carriers, radioactive preparations in vivo, introduction of heterocyclic compound isotopes, etc., can solve the problems of inability to realize dynamic research, unfavorable dynamic research, complicated operation, etc., and achieve good biological distribution characteristics, The effect of good pharmacokinetic characteristics and accurate test results

Active Publication Date: 2016-10-12
上海准视生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although in vitro detection methods can judge and analyze the expression level of C-MET in cells or tissues, there are certain limitations in terms of technical analysis: ① Specimens need to be obtained through cell culture, biopsy or autopsy, and cannot be directly applied to the human body ;②The results of in vitro experiments may not be consistent with the real situation in the living body: In vitro experiments are greatly affected by experimental conditions, experimental equipment, and experimental methods. During the processing of samples, some important components may be lost, resulting in large errors , so that the experimental results are inconsistent with the real situation in the living body; ③ in vitro experiments are not con

Method used

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  • Radioactive C-MET-targeted affinity micromolecular compound and application thereof
  • Radioactive C-MET-targeted affinity micromolecular compound and application thereof
  • Radioactive C-MET-targeted affinity micromolecular compound and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0049] Example 1:

[0050] 1) 18 Synthesis and characterization of F-cMET-1 probe;

[0051]

[0052] Reagent: 4mg cMET-1, K 18 F, K 222 / K 2 CO 3 Solution( 18 For F labeling, containing 15mgK 222 And 3.5mgK 2 CO 3 Per ml), dry DMSO.

[0053] Operation process:

[0054] Use standard 18 F radioactive labeling reactor for labeling. Specifically, the K now prepared by the particle accelerator 18 F(K 2 CO 3 Zhonghe H 18 F produced), add 1mLK 222 / K 2 CO 3 Solution, add 1mL acetonitrile and stir, pass N 2 , Heat to 85 ℃ to blow dry the solvent, then repeat adding 1mL acetonitrile and blow dry twice (total 3 times), remove the K 18 The water in F. Take 4mg of CMET-1 reactant and dissolve it in 1mL of anhydrous DMSO. 2 Add the reactor under protection and heat to 110°C to react for 30 minutes. Preparative HPLC separation and purification 18 F-cMET-1. 1 H NMR(300MHz, CDCl 3 )δ8.85(d,J=2.6Hz,1H),8.31(s,1H),8.24-8.10(m,1H),7.84-7.67(m,2H),7.57(t,J=7.9Hz,1H ),7.35(s,1H),6.66(s,1H),5.45-5.17(m,...

Example Embodiment

[0063] Example 2:

[0064] 1) 68 Synthesis and characterization of Ga-NODAGA-cMET-1 probe;

[0065]

[0066] Add NODAGA-cMET-1 to the content 68 In the ethanol solution of Ga radioisotope, adjust the pH to a suitable value, react for 30 minutes, and then use a C18 elution column to rinse out the product, and the radioactivity detector detects and labels successfully.

[0067] 2) Glioma 68 Ga-NODAGA-cMET-1 in vivo molecular imaging

[0068] Establish a subcutaneous transplantation tumor model of nude mouse glioma (U87MG), probe 68 One hour after Ga-NODAGA-cMET-1 injection, a 5-minute static PET imaging scan combined with CT scan was performed. The result is Figure 4 . 68 Ga-NODAGA-cMET-1 was significantly aggregated at the tumor site 2 hours after intravenous injection, while the probe did not aggregate in the control group OVCAR3 tumor (C-MET expression negative). After a large amount of unlabeled NODAGA-cMET-1 was blocked, the amount of probe aggregation in the tumor was significan...

Example Embodiment

[0071] Example 3

[0072] 1) 18 Synthesis and characterization of F-cMET-2 probe;

[0073]

[0074] Reagent: 4mg cMET-2, K 18 F, K 222 / K 2 CO 3 Solution( 18 For F labeling, containing 15mgK 222 And 3.5mgK 2 CO 3 Per ml), dry DMSO.

[0075] Operation process:

[0076] Use standard 18 F radioactive labeling reactor for labeling. Specifically, the K now prepared by the particle accelerator 18 F(K 2 CO 3 Zhonghe H 18 F produced), add 1mLK 222 / K 2 CO 3 Solution, add 1mL acetonitrile and stir, pass N 2 , Heat to 85 ℃ to blow dry the solvent, then repeat adding 1mL acetonitrile and blow dry twice (total 3 times), remove the K 18 The water in F. Take 4mg of CMET-2 reactant and dissolve it in 1mL of anhydrous DMSO, and mix it evenly. 2 Add the reactor under protection and heat to 110°C to react for 30 minutes. Preparative HPLC separation and purification 18 F-CMET-2. 1 H NMR (300MHz, Chloroform-d) δ8.78 (d, J=2.7Hz, 1H), 7.71 (s, 1H), 7.24-7.21 (m, 1H), 6.87 (s, 1H), 5.35-5.19 ( m, 1H), 4...

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Abstract

The invention especially relates to a radioactive C-MET-targeted affinity micromolecular compound and application thereof, belonging to the field of medical diagnosis and treatment. According to the invention, in-vivo tracking and imaging of diseases like tumors is realized through radiolabeling of a C-MET receptor antagonist. The radioactive C-MET-targeted affinity micromolecular compound can be used for monitoring the characteristics of biochemical changes of a hepatocyte growth factor receptor, visually displays the distribution and quantity of C-MET and is applicable to specific detection of a plurality of cancers including glioma, lung cancer, prostatic cancer, breast cancer, esophagus cancer, stomach cancer, liver cancer, pancreas cancer, ovarian cancer, rectal cancer and cervical cancer. The radioactive C-MET-targeted affinity micromolecular compound also has certain anticancer activity and has wide clinical application prospect.

Description

technical field [0001] The invention belongs to the field of medical diagnosis and treatment, in particular to a radioactive C-MET targeting affinity small molecular compound and its application. Background technique [0002] The encoded product of the proto-oncogene hepatocyte growth factor receptor (c-MET) is the cell membrane receptor of hepatocyte growth factor (HGF), which belongs to the tyrosine kinase receptor. The body dimerization leads to the activation of a series of signaling pathways, which lead to tumor angiogenesis, proliferation, enhanced cell motility and invasion, and finally metastasis. Therefore, the interaction between C-MET and its ligand HGF is closely related to the occurrence of various human tumors. , development related. Existing studies have found that C-MET receptors are highly expressed in a variety of tumors, including glioma, lung cancer, prostate cancer, breast cancer, esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, ovari...

Claims

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Application Information

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IPC IPC(8): C07D215/38C07D401/12C07B59/00A61K51/04A61P35/00A61K101/02
CPCA61K51/0455C07B59/002C07B2200/05C07D215/38C07D401/12
Inventor 程震张翱申宝忠卜丽红陈浩
Owner 上海准视生物科技有限公司
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