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Radionuclide labeled FAPI compound and synthesis process method thereof

A radionuclide and synthesis process technology, applied in the field of radionuclide-labeled FAPI compounds and their synthesis processes, can solve the problems of limited clinical promotion, inability to achieve mass production and distribution, and low primary output, and achieves the ability to meet clinical needs. Effect

Pending Publication Date: 2021-06-11
上海市质子重离子临床技术研发中心
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In recent years, quinoline-based small molecule FAP inhibitors (FAPinhibitor, FAPI) have shown excellent FAP affinity, a variety of 68 Ga-FAPI has also shown a high degree of tumor uptake and rapid clearance in vivo in animal experiments, and is very suitable for in vivo imaging. At present, various domestic clinical hospitals use metal nuclides 68 Compounds of Ga-labeled FAPI, due to 68 Ga is produced by a generator, with a low yield and a short half-life (only 68 minutes), making it impossible to achieve mass production and distribution, which greatly limits clinical promotion

Method used

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  • Radionuclide labeled FAPI compound and synthesis process method thereof
  • Radionuclide labeled FAPI compound and synthesis process method thereof
  • Radionuclide labeled FAPI compound and synthesis process method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0030] This embodiment relates to a compound Al of radionuclide-labeled FAPI 18 F-FAPI synthesis process method, wherein Al 18 The chemical structural formula of F-FAPI is:

[0031]

[0032] This example is intended to synthesize liquid nuclides 18 F-marked FAPI ( 18 F-FAPI), specifically, using Al 3 + ion pair 18 Strong complexation and bridging of F ions and cyclic coordination groups (DOTA and NOTA) to synthesize Al with longer half-life 18 F-FAPI to achieve Al 18 F-FAPI has a synthesis process of more than 99% radiochemical purity and a single yield greater than 100mCi, which meets clinical needs.

[0033] Al given in this example 18 The specific process synthesis steps of F-FAPI include:

[0034] (1) Raw material preparation stage: prepare the following doses of raw materials, including:

[0035] Reagent name dose Methyl sulfoxide (DMSO) 300μL 0.5mol / L NaOAc 0.3mL 10mmol / L AlCl 3

6μL 4mmol / L FAPI-04 20 μL Absol...

Embodiment 2

[0050] Embodiment 1 obtains the quality control method of product:

[0051] (1) Physical and chemical properties:

[0052] Color: colorless

[0053] Properties: transparent clear liquid

[0054] pH value: 4.0~6.0

[0055] (2) Radiochemical purity test:

[0056] TLC quality control:

[0057] Using 0.1mol / L sodium acetate solution as developing agent, TLC was carried out to obtain quality control results:

[0058] Depend on figure 1 As shown, the product only exists at the origin position (obvious radioactive peak), but no radioactive peak appears at the front end (70mm-80mm), indicating that Al 18 The radiochemical purity of F-FAPI is close to 100%.

[0059] HPLC quality control:

[0060] The composition of the product was determined by high performance liquid chromatography (HPLC), and the detection parameters: ① column length: 200mm; ② column diameter: 4.6mm; ③ column packing C18; ④ mobile phase: A phase: water, B phase: acetonitrile, gradient elution: 0~10min from 95%...

Embodiment 3

[0062] Embodiment 3: the product that embodiment 1 obtains is used for biological experiment effect

[0063] (1) Experiment 1:

[0064] Product stability test in vitro:

[0065] A certain amount of the product was added to PBS and fresh mouse serum respectively, and the radiochemical purity was measured at different time points of 0, 0.5h, 1h, 2h, and 4h to detect the stability of the product. see results image 3 , 4h later, the radiochemical purity of the products was greater than 95%, indicating that they maintained high stability.

[0066] (2) Experiment 2:

[0067] In vivo distribution experiment in tumor-bearing nude mice:

[0068] Twelve female BALB / c-nu / nu mice, 6 weeks old, weighing about 20g, subcutaneously inoculated about 1×107 cells of SK-LMS-1 in the right leg, and injected them through the tail vein of the mice after the tumor volume reached about 1cm3 Product, 20uCi / mouse, select four time points (0.5h, 1h, 1.5h, 2h) after injection, execute 3 tumor-bearin...

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Abstract

According to the invention, liquid nuclide < 18 > F-labeled FAPI (< 18 > F-FAPI) is fitted, specifically, the < 18 > F-FAPI with a relatively long half-life period is synthesized by utilizing a strong complexing and bridging effect of Al < 3 + > ions on < 18 > F ions and cyclic coordination groups (DOTA and NOTA), and a radiochemical purity synthesis process of the Al< 18 > F-FAPI of 99% or above and a single yield of more than 100 mCi are realized, so that clinical requirements are met.

Description

technical field [0001] The invention relates to the technical field of nuclear medicine, in particular to a radionuclide-labeled FAPI compound and a synthesis process thereof Background technique [0002] Tumor-associated fibroblasts highly express fibroblast activation protein (fibroblast activation protein, FAP), but normal tissues and normal fibroblasts do not express FAP, so FAP has become a potential specific target for tumor diagnosis and treatment. In recent years, quinoline-based small molecule FAP inhibitors (FAPinhibitor, FAPI) have shown excellent FAP affinity, a variety of 68 Ga-FAPI has also shown a high degree of tumor uptake and rapid clearance in vivo in animal experiments, and is very suitable for in vivo imaging. At present, various domestic clinical hospitals use metal nuclides 68 Compounds of Ga-labeled FAPI, due to 68 Ga is produced by a generator with a low primary yield and a short half-life (only 68 minutes), making it impossible to achieve mass pro...

Claims

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Application Information

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IPC IPC(8): A61K51/04C07D401/14A61K101/02
CPCA61K51/0482C07D401/14
Inventor 李自立孙筠程竞仪刘明玉刘正旺刘成马光
Owner 上海市质子重离子临床技术研发中心
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