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3-18F-fluorolactic acid analogue as well as preparation method and application thereof

An analog, lactic acid technology, applied in the fields of medicinal chemistry and nuclear medicine, can solve the problems of unsuitable molecular probe production, limitation, short half-life, etc., and achieve the effect of fast blood clearance rate, stable labeling rate, and good biodistribution characteristics

Active Publication Date: 2018-06-22
上海释雅医药科技有限公司
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AI Technical Summary

Problems solved by technology

However 3- 11 C-lactic acid is passed 11 C-iodomethane and corresponding substrates are prepared under the catalysis of enzymes, this method is not suitable for the production of conventional molecular probes, and 11 C shorter half-life (t 1 / 2 =20min), limiting the 3- 11 Further clinical application of C-lactic acid

Method used

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  • 3-18F-fluorolactic acid analogue as well as preparation method and application thereof
  • 3-18F-fluorolactic acid analogue as well as preparation method and application thereof
  • 3-18F-fluorolactic acid analogue as well as preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1、3-18

[0034] Example 1, 3-[18F] Fluoro-2-hydroxy-propionic acid (R in formula A 1 as hydrogen) synthesis

[0035] Use 1 ml of acetonitrile aqueous solution containing 3.6 mg of cesium carbonate and 40 mg of aminopolyether K222 to elute 18F- into the reaction flask, evaporate to dryness under negative pressure at 110 °C, and add 1.0 mL of anhydrous acetonitrile to evaporate to dryness. 20 mg of the precursor compound 2,3-epoxy propionate methyl ester (in formula B, R 1 for hydrogen, R 2 Methyl) was dissolved in 1 mL of anhydrous tert-amyl alcohol, added to the reaction flask, sealed and heated, and reacted at 120° C. for 20 min. After the reaction, it was cooled to room temperature, injected into a reverse-phase C18 semi-preparative column (5 μm, 250 × 10 mm, product of YMC Corporation of Japan), and the components with a retention time of 7.5 to 9.0 min were collected as the fluorine-18-labeled intermediate, that is, formula C Intermediate shown, R 1 for hydrogen, R 2is methyl;...

Embodiment 2、3-18

[0036] Example 2, Biodistribution test of 3-[18F]fluoro-2-hydroxyl-propionic acid

[0037] Preparation of tumor mouse model: After diluting the S180 ascites cells taken from the peritoneal cavity of the mouse by 2 times with normal saline, inject 0.2ml subcutaneously in the right lower limb of the ICR mouse, a solid tumor can be formed in 7 days, and then the compound can be used for biological evaluation and evaluation. Used in Micro-PET imaging experiments.

[0038] To 4 S180 tumor model ICR mice, 74 kBq of 3-[18F]fluoro-2-hydroxy-propionic acid injection prepared in Example 1 were injected into the tail vein respectively, and PET imaging was performed at 60 minutes, and they were executed after the imaging was completed. Dissect and take the organs and tissues of interest: blood, heart, liver, lung, kidney, stomach, large intestine, small intestine, bone, muscle, tumor, brain, etc., weigh and count them respectively, and perform decay correction on each tissue sample The c...

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Abstract

The invention discloses a 3-18F-fluorolactic acid analogue as well as a preparation method and application thereof. The structural formula of the fluoro-18 marked lactic acid analogue is shown by formula A, where R1 is hydrogen or C1-C4 alkyl. The lactic acid analogue can be prepared by the following method: in the presence of amino polyether serving as a phase transfer catalyst and a basic catalyst, the compound shown by formula B and the 18F ions are subjected to nucleophilic addition to obtain an intermediate shown by formula C; in an alkaline condition, hydrolyzing the intermediate shown by the formula C to obtain the 3-18F-fluorolactic acid analogue. Compared with the prior art, the fluoro-18 marked lactic acid analogue provided by the invention has an exact characteristic of uptake by tumor, and also has relatively good bio-distribution feature, the potential of serving as a tumor developer, and the characteristics of easiness in preparation and stable labeling rate. Therefore, the fluoro-18 marked lactic acid analogue can be employed as a tumor lactic acid metabolism PET development molecular probe, and has high sensitivity and good selectivity.

Description

technical field [0001] The present invention relates to a 3- 18 F-fluorinated lactic acid analogs and a preparation method and application thereof belong to the technical fields of medicinal chemistry and nuclear medicine. Background technique [0002] Glucose is the main substance for tumor cells to obtain energy. In order to meet their rapid growth requirements for energy and other nutrients, tumor cells selectively pass through aerobic glycolysis, making lactic acid the main product of tumor cells’ glucose metabolism. . However, the existence and further metabolism of a large amount of lactate are closely related to tumor invasion and metastasis, angiogenesis, immune escape, radiotherapy resistance, and induced drug resistance. Previous studies on tumor lactate have focused on the production and accumulation of lactate. Recent studies have confirmed that in the oxygen-rich area of ​​tumors, tumor cells can not only take up lactate, but also convert it into pyruvate and ...

Claims

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Application Information

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IPC IPC(8): C07C27/02C07C59/115C07C67/31C07C69/675C07B59/00A61K51/04A61K101/02
CPCA61K51/0402C07B59/001C07B2200/05C07C59/115
Inventor 王红亮武志芳李思进马晶鑫刘海燕陆克义董伟璇
Owner 上海释雅医药科技有限公司
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