A 3- 18 f-Fluorolactic acid analogue and its preparation method and application

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

Active Publication Date: 2020-09-25
上海释雅医药科技有限公司
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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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  • A 3- <sup>18</sup> f-Fluorolactic acid analogue and its preparation method and application
  • A 3- <sup>18</sup> f-Fluorolactic acid analogue and its preparation method and application
  • A 3- <sup>18</sup> f-Fluorolactic acid analogue and its preparation method and application

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Experimental program
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Effect test

Embodiment 1、3-18

[0034] Embodiment 1, 3-[18F] fluoro-2-hydroxyl-propionic acid (R in formula A 1 for the synthesis of hydrogen)

[0035] Use 1ml of acetonitrile aqueous solution containing 3.6mg of cesium carbonate and 40mg of amino polyether K222 to elute 18F- into the reaction flask, evaporate to dryness at 110°C under negative pressure, add 1.0mL of anhydrous acetonitrile and evaporate to dryness. 20 mg of the precursor compound methyl 2,3-epoxy propionate (in the formula B, R 1 for hydrogen, R 2 (methyl) was dissolved in 1 mL of anhydrous tert-amyl alcohol, added to the reaction bottle, sealed and heated, and reacted at 120°C for 20 min. After the reaction is finished, cool to room temperature, inject into a reversed-phase C18 semi-preparative column (5 μm, 250×10 mm, product of YMC Company, Japan), and collect the component with a retention time of 7.5 to 9.0 min, which is the fluorine-18 labeled intermediate, namely the formula C The indicated intermediate, R 1 for hydrogen, R2 is me...

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, 74kBq of 3-[18F]fluoro-2-hydroxy-propionic acid injection prepared in Example 1 were injected into the tail vein respectively, 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 counts...

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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 The invention relates to an F-fluorolactic acid analogue and a preparation method and application thereof, belonging 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 rapidly growing demand for energy and other nutrients, tumor cells selectively undergo aerobic glycolysis, making lactic acid the main product of tumor cell glucose metabolism. . However, the existence and further metabolism of a large amount of lactic acid are closely related to tumor invasion and metastasis, angiogenesis, immune escape, radiotherapy resistance, and drug resistance induction. Previous research on lactate in tumors focused on the generation and accumulation of lactate. Recent studies have confirmed that in oxygen-rich areas of tumors, tumor cells can not only take up lactate, but also convert it ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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