18 F-labeled egfr positron imaging agent and preparation method and application thereof

A semi-preparation and reaction technology, applied in the field of 18F-labeled EGFR positron imaging agent and its preparation, to achieve fast clearance in vivo, good specificity, and good tracer effect

Active Publication Date: 2022-07-05
NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, studies have shown that EGFR-TKIs are mutation-sensitive, and not all patients with high EGFR expression can benefit. Therefore, the screening of EGFR-TKIs-sensitive patients is a clinical problem that needs to be solved urgently

Method used

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  • <sup>18</sup> F-labeled egfr positron imaging agent and preparation method and application thereof
  • <sup>18</sup> F-labeled egfr positron imaging agent and preparation method and application thereof
  • <sup>18</sup> F-labeled egfr positron imaging agent and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0087] The compound represented by the formula (III) in Example 1 ( 18 Preparation method of F-labeled EGFR positron imaging agent precursor)

[0088] 4-Chloro-6,7-bis(2-methoxyethoxy)quinazoline (formula (V), 40.00g, 1eq), DMF (N,N-dimethylformaldehyde) were successively added to the 500mL three-necked flask. amide, 200 mL), potassium carbonate (35.38 g, 2 eq), propargylamine (8.48 g, 1.2 eq), stirred at 90° C. for 2.5 h. After the completion of the reaction monitored by TLC (thin layer chromatography), the temperature was lowered to room temperature (20-30° C.), 400 mL of water was added, and the mixture was stirred uniformly. Filter and wash twice with 400 mL of water. The filter cake was spin-dried to obtain 24.5 g of a silver-white solid product (formula (VI)) with a yield of 57.8%.

[0089] 4-propargylamino-6,7-bis(2-methoxyethoxy)quinazoline (formula (VI), 0.42g, 1.0 eq), copper sulfate pentahydrate (0.018g) were successively added to the reaction flask. , 0.05eq), ...

Embodiment 2

[0091] The compound represented by the formula (IV) of Example 2 ( 18 Preparation method of F-labeled EGFR positron imaging agent standard)

[0092] 4-Chloro-6,7-bis(2-methoxyethoxy)quinazoline (formula (V), 40.00g, 1eq), DMF (N,N-dimethylformaldehyde) were successively added to the 500mL three-necked flask. amide, 200 mL, 5V), potassium carbonate (35.38 g, 2 eq), propargylamine (8.48 g, 1.2 eq), stirred at 90 °C for 2.5 h. TLC (thin layer chromatography) monitoring after the completion of the reaction, the temperature was lowered to room temperature (20-30° C.), 400 mL (10 V) of water was added, and the mixture was stirred uniformly. Filter and wash twice with 400 ml of water. The filter cake was spin-dried to obtain 24.5 g of a silver-white solid product (formula (VI)) with a yield of 57.8%.

[0093] 4-propargylamino-6,7-bis(2-methoxyethoxy)quinazoline (formula (VI), 2.70g, 1.0eq), copper sulfate pentahydrate (0.40g) were successively added to the reaction flask. , 0.2eq...

Embodiment 3

[0095] The compound represented by the formula (II) in Example 3 ( 18 Preparation method of F-labeled EGFR positron imaging agent)

[0096] (1) bombarding H with a medical cyclotron 2 18 O, through 18 O(p,n) 18 F nuclear reaction produces 500mCi 18 F, and conduct it in an anion exchange column, measure the activity and use 1.5 mL of mixed solution (15.0 mg of 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8] 2 Hexane (K 2.2.2. ) plus 4.5mg K 2 CO 3 Dissolved in 0.15mL water and 1.35mL acetonitrile) 18 F rinsed into the reaction flask;

[0097] (2) High-purity helium gas was continuously blown into the reaction flask, water was removed azeotropically for 3 minutes at 110 °C, and dried; 5 mg of the precursor was dissolved in 1 mL of anhydrous DMSO solution, added to the reaction flask, and reacted at 110 °C for 15 min.

[0098] (3) after cooling the reaction solution, carry out semi-preparative HPLC separation to obtain 18 F-labeled EGFR positron imaging agent, the separ...

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Abstract

The invention belongs to the technical field of medicinal chemistry and nuclear pharmacy, and discloses 18 F-labeled EGFR positron imaging agent and preparation method and application thereof. Should 18 The F-labeled EGFR positron imaging agent has the structure shown in formula (II), formula (II). It has good tracking effect and good specificity, and can positively identify epidermal factor receptor (EGFR) highly expressed or mutant tumors; at the same time, the compound has good stability in vitro, is mainly metabolized by the intestine, gallbladder and kidney, and is rapidly cleared in vivo. , muscle, bone, heart, lung, liver and other background organs and tissues have low background uptake, and can be used as tumor PET imaging agent, EGFR expression level detection agent, and EGFR inhibitor screening agent.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry and nuclear pharmacy, and specifically relates to 18 F-labeled EGFR positron imaging agent and preparation method and application thereof. Background technique [0002] Positron Emission Tomograghy ​​(PET) is currently the best imaging equipment for monitoring the occurrence and development of tumors in vivo. , Non-invasive, three-dimensional, dynamic study of biochemical process, PET can be used in tumor diagnosis, benign and malignant differentiation, malignant tumor staging, classification and early diagnosis and identification of tumor recurrence and metastasis, selection of treatment plan and effect of chemotherapy and radiotherapy. Detection and observation of tumor changes and monitoring of prognosis. [0003] Epidermal growth factor receptor (EGFR) is a huge transmembrane glycoprotein with a molecular weight of about 180kDa and has ligand-induced tyrosine protein kinase activ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D403/12C07B59/00A61K51/04A61K101/02
CPCC07D403/12C07B59/002A61K51/0459C07B2200/05Y02P20/55
Inventor 黄顺韩彦江胡孔珍吴湖炳唐刚华
Owner NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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