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{0><}0{>Radio-labeled tumor developing agent as well as preparation method and application thereof

A tumor imaging agent and labeling technology, applied in the field of medical imaging, can solve problems such as weak amino acid targeting, and achieve the effects of good biological evaluation effect, efficient response, and short labeling time.

Active Publication Date: 2016-09-28
XIAMEN UNIV
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  • Claims
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Problems solved by technology

[0010] The purpose of the present invention is to overcome the problems of weak targeting of amino acids and high intake of folic acid in the kidney, and at the same time have the advantages of high tumor uptake of amino acids and targeted uptake of folic acid in tumors, and provide a combination of folic acid and α -Amino acid derivative coupled 18 F-labeled tumor imaging agent, its preparation method and application, and its use in the diagnosis or curative effect evaluation of tumor or other diseases by PET imaging

Method used

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  • {0&gt;&lt;}0{&gt;Radio-labeled tumor developing agent as well as preparation method and application thereof
  • {0&gt;&lt;}0{&gt;Radio-labeled tumor developing agent as well as preparation method and application thereof
  • {0&gt;&lt;}0{&gt;Radio-labeled tumor developing agent as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Embodiment 1: the synthesis of labeling precursor namely compound 7-1 and compound 7-2

[0050] 1) In 10ml of tetrahydrofuran, add compound 1 (0.99g, 0.01mol), compound 2 (1.45g, 0.012mol), add tetraethoxytitanium (4.56g, 0.02mol), stir and react at room temperature overnight; add 10ml After diluting with ethyl acetate, add 10ml of saturated sodium chloride solution to quench, stir for 5min, filter through celite to remove insoluble matter, take the organic phase of the filtrate, wash with saturated sodium chloride solution, dry over anhydrous sodium sulfate, remove the solvent, The crude product was eluted with a dichloromethane-ethyl acetate mixture with a volume ratio of 10-20:1 and purified by silica gel column chromatography to obtain compound 3, 1.63 g;

[0051] 2) In the glove box, compound 3 (0.2 g, 1 mmol) was added to 2 ml of toluene; another compound 4 (0.51 g, 2 mmol) was dissolved in 2 mL of toluene, and added to the solution containing compound 3; then (1 ...

Embodiment 2

[0054] Example 2: 18 Preparation of F-labeled tumor imaging agent, compound 9

[0055] (1) Preparation of compound 7-2

[0056] a) will 18 F is eluted from the anion trapping column QMA with a mixed solution of potassium carbonate and Kriptofix 2.2.2 (K2.2.2) (mass ratio 5:1) to obtain a K of 5-20 mCi 18 F aqueous solution;

[0057] b) Add 7.5 μL of pyridazine-hydrochloride buffer solution with a pH of 2.5, 7.5 μL of N,N-dimethylformamide, and compound 7-1 prepared in Example 1, 1 mg, into a 1.5 mL centrifuge tube;

[0058] c) the K obtained in step a) 18 F aqueous solution (5~20mCi, 10μL) was added to the solution in step b), heated to 60°C for 10min, cooled, and then diluted with 2ml of deionized water, followed by C18Sep-Pak cartridge column chromatography, first deionized with 2ml Deionized water was used to remove impurities, and then the product was rinsed with a mixture of 0.5ml boric acid and 1ml of PBS-ethanol solution with a volume ratio of 1:1 as the eluent to ...

Embodiment 3

[0060] Example 3: 18 Biodistribution of F-labeled tumor imaging agent (compound 9)

[0061] Select 18-20g nude mice, and inject about 5×10 cells into the axilla of the forelimb of the nude mice 6 KB cell fluid modeling. During the first week of the experiment, folic acid-deficient food should be used for feeding. Each mouse is prepared by tail vein injection of Example 2 18 The F-labeled tumor imaging agent is compound 9, the injection dose is 10μCi / 100μL (normal saline), and it is executed 1h and 2h after administration, and the blood, heart, liver, lung, kidney and other major organs are collected, weighed and counted . In the folate-suppressed control group, after injection 18 The F-labeled tumor imaging agent was injected with 100 μg folic acid 10 minutes before inhibition, and the mice were sacrificed 2 hours after the administration, and the main organs were also weighed and counted. The results are detailed in Tables 1 and 2.

[0062] It can be seen from Table 1 ...

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Abstract

{0><}0{>The invention discloses a radio-labeled tumor developing agent as well as a preparation method and application thereof. <0}{0><}0{>The radio-labeled tumor developing agent structurally contains an alpha-amino acid derivate structure capable of labeling nuclide and a tumor-targeted folic acid molecule, wherein radionuclide is 18F, and the alpha-amino acid derivate structure and the folic acid molecule are connected in a specific chemical mode. <0}{0><}0{>The invention further relates to a preparation method of the compound and application of the compound serving as a tracing developing agent in PET development in a human body or an animal body. The radio-labeled tumor developing agent has the advantages of simplicity in preparation, low price and strong targeting property especially when serving as a tumor developing agent.

Description

technical field [0001] The invention belongs to the technical field of medical imaging, and specifically relates to a 18 F-labeled tumor imaging agent, its preparation method and application. Background technique [0002] α-Amino acids are the building blocks of proteins and play crucial roles in neurotransmitters and ATP energy conversion. α-amino acid is also an essential nutrient for the survival and proliferation of tumor cells. Most tumors have a high uptake of amino acids, which in turn will lead to higher uptake of high-grade tumors and tumor metastasis. Amino acids are signaling molecules for tumor proliferation and also play a role in the biomass accumulation of tumor-associated reprogrammed metabolic networks. [0003] In addition, folate receptors are highly expressed in many tumor tissues, such as ovarian cancer, kidney cancer, uterine cancer, testicular cancer, brain cancer, colon cancer, lung adenocarcinoma and so on. The folic acid molecule is highly select...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K51/04C07F5/02A61K101/02
CPCA61K51/0459A61K51/0497C07B2200/05C07F5/02
Inventor 张现忠李化黄路梅季悦李子婧郭志德陈小元
Owner XIAMEN UNIV
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