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PET tracer agent precursor-2-nitroimidazole compound and preparation method thereof

A nitroimidazole and tracer technology, applied in the field of radiopharmaceutical synthesis, can solve the problems of inability to guarantee specific imaging activity, poor image clarity, low target/background value, etc., and achieves rapid tissue penetration, Short imaging time interval, evenly distributed effect

Inactive Publication Date: 2016-07-13
JIANGSU PROVINCE HOSPITAL
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the above methods usually involve multi-step synthesis and purification, and the total synthesis time is about 1-3 hours. Compared with nuclides with short half-lives, sufficient specific activity cannot be guaranteed for imaging, and the image clarity is not good.
On the other hand, existing hypoxic imaging agents generally have neurotoxicity and soft tissue absorption in terms of biological properties, slow concentration in tumors, and low target / background values

Method used

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  • PET tracer agent precursor-2-nitroimidazole compound and preparation method thereof
  • PET tracer agent precursor-2-nitroimidazole compound and preparation method thereof
  • PET tracer agent precursor-2-nitroimidazole compound and preparation method thereof

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Experimental program
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Effect test

Embodiment 1

[0029] Embodiment 1: the preparation of NOTA-Nitro1:

[0030] (1) Preparation of 1,4-bis(tert-butoxycarbonylmethyl)1,4,7-triazacyclononane: tert-butyl bromoacetate (21.4g, 55mmol) was dissolved in CHCl 3 (100mL), at room temperature, add 1,4,7-triazacyclononane (6.5g, 50mmol) in CHCl using a syringe pump for 1h 3 (50mL) solution for 24h. After filtration, the filtrate was evaporated to dryness, 50 mL of distilled water was added, and the pH was adjusted to 3 with 1M HCl. Extracted 3 times with 50 mL ether. The organic layer was evaporated to dryness to obtain the tri-tert-butoxycarbonylmethyl substitution of 1,4,7-triazacyclononane. The aqueous layer was adjusted to pH 11 with 1M NaOH. With 50mLCH 2 Cl 2 Extracted three times, combined the organic phases, added n-hexane for recrystallization, and obtained the disubstituted product 1,4-bis(tert-butoxycarbonylmethyl)1,4,7-triazacyclononane. The yield was 61%.

[0031] (2) Preparation of tert-butyl 2-(2-nitro-1H-imidazol-...

Embodiment 2

[0037] Embodiment 2: the preparation of PET tracer 18F-FAl-NOTA-Nitro1

[0038] (1) Preparation of 18F solution: Proton velocity bombardment of H in a medical accelerator 2 18 get 18 F solution. Using CRC-15R activity meter (CAPINTEC) to measure the radiation dose was 20mCi.

[0039] (2) Preparation of PET tracer 18F-FAl-NOTA-Nitro1: Take the precursor NOTA-Nitro10.1 mg prepared in Example 1 in a vial, add 10 μL of glacial acetic acid, 0.005 mg of aluminum trichloride (acetic acid / acetic acid Dissolve in sodium buffer solution), 200 μL acetonitrile, continue to add 50 μL 18F ionic solution, and react in a closed manner at 100°C for 20 minutes. After the reaction is completed, cool to room temperature and then add ultrapure water, let the reaction solution pressurize through the pre-activated aluminum chloride column, The unreacted 18F ions are adsorbed, the eluate is collected, and the used solution is removed by heating, and the target product is obtained by dissolving wi...

Embodiment 3

[0042] Embodiment 3: MicroPET imaging test

[0043] Model mice bearing human transplanted tumors (ECa109 esophageal carcinoma) were placed on small animal PET beds, anesthetized with isoflurane, and fixed with adhesive tape. The model mice were injected with the tracer physiological saline solution (1.85 MBq, 0.2 ml) prepared in Example 2 above through the tail vein. Dynamic scanning was performed 2 hours after injection, and MicroPET imaging was performed respectively. The results were as follows: image 3 shown.

[0044] The image reconstruction is carried out by two-dimensional ordered subset expectation maximization method. Calculate the radioactivity (MBq / ml) in the tumor, muscle, liver and other organs with the region of interest (ROI) method, and divide the obtained value by the injected dose to obtain the PET tracer uptake value (%ID / g) of each tissue (assumed The tissue density is 1 g / ml). The calculation results are as Figure 4 shown. The target / non-target rat...

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Abstract

The invention relates to a PET tracer agent precursor-2-nitroimidazole compound and a preparation method thereof.The chemical name of the precursor is 2-[4-(carboxymethyl)-7-[2-(2-(2-nitro-1H-imidazole-1-yl)acetylamino)ethyl]-1,4,7-triazacyclononane-1-yl]acetic acid, and the structural formula of the precursor is shown as a formula (I) (please see the formula in the description).The PET tracer agent precursor solves the technical problems that an existing hypoxic imaging agent is complex in labeling operation and low in labeling rate, overcomes the high lipophilicity application defect and is particularly suitable for diagnosis, treatment, treatment effect monitoring and the like of hypoxic tumors.

Description

technical field [0001] The invention relates to a PET tracer precursor, in particular to a nitroimidazole compound and a preparation method thereof, and belongs to the technical field of radiopharmaceutical synthesis. Background technique [0002] The application of positron emission tomography (PET) in tumor diagnosis and treatment is mainly because most malignant tumors have high metabolism or high expression tendency to glucose, protein, nucleic acid, oxygen and other substances. PET imaging technology uses glucose, protein, nucleic acid and other small molecules as carriers to label positron radioactive nuclides (such as 18F, 11C, 13N, 15O, 64Cu or 68Ga, etc.) with a short half-life as tracers and inject them into the human body. Followed by blood circulation concentrated to the target site of the organ. The PET detection system collects two gamma photons with the same energy (511keV) and opposite directions produced by the annihilation radiation of each positron nuclid...

Claims

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Application Information

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IPC IPC(8): C07D403/12A61K51/04
CPCA61K51/044C07D403/12Y02P20/55
Inventor 孙新臣鲁璟杨曦成红艳唐心宇葛小林许礼平
Owner JIANGSU PROVINCE HOSPITAL
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