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A FAP-α specific tumor diagnostic spect imaging agent

A kit and radionuclide technology, applied in the field of broad-spectrum tumor SPECT imaging agents targeting FAP-α, can solve the problems of expensive equipment, drugs and inspections, low targeting specificity, and poor imaging effects , to achieve excellent in vivo biodistribution, high tumor uptake and tumor/organ uptake ratio, and good druggability

Active Publication Date: 2021-05-18
嘉兴法伯新天医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Compared with the two, PET diagnosis has significant advantages in detection sensitivity, image resolution and clarity, and positioning accuracy, but its equipment, drugs and examination costs are more expensive
However, there are few types of tumor-specific SPECT imaging agents currently used clinically, the targeting specificity is not high, and the imaging effect is poor. Therefore, it is necessary to vigorously develop broad-spectrum tumor-specific SPECT imaging technology

Method used

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  • A FAP-α specific tumor diagnostic spect imaging agent
  • A FAP-α specific tumor diagnostic spect imaging agent
  • A FAP-α specific tumor diagnostic spect imaging agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Example 1 Chemical synthesis of HFAPi and HpFAPi

[0056] Method 1 for separating and purifying the target product by high performance liquid chromatography: Agilent 1260 HPLC system is equipped with YMC-Pack ODS-A C18 semi-preparative column (250×10mml.D.S-5μm, 12nm). Gradient elution for 25min, flow rate 3.2mL / min, wherein mobile phase A is deionized water (containing 0.05% TFA), mobile phase B is acetonitrile (containing 0.05% TFA), elution gradient is set to 85% A at the beginning and 15%B, 85%A and 15%B at 5min, 45%A and 55%B at 25min.

[0057] Method 2 for separating and purifying the target product by high performance liquid chromatography: Agilent 1260 HPLC system was equipped with YMC-Pack ODS-A C18 semi-preparative column (250×10mml.D.S-5μm, 12nm). Gradient elution for 25min, flow rate 2.0mL / min, wherein mobile phase A is deionized water (containing 0.05% TFA), mobile phase B is acetonitrile (containing 0.05% TFA), elution gradient is set to 80% A at the begi...

Embodiment 2

[0094] Example 2 Preparation of HFAPi and HpFAPi lyophilized labeling kits

[0095] (1) Preparation of HFAPi kit

[0096] Weigh 1 mg of HFAPi and dissolve it in 1 mL of 75% ethanol in water with a concentration of 1 μg / μL; then prepare a mixed solution containing 25 μg (25 μL) of HFAPi, 2.0 mg of Tricine, 3.0 mg of TPPTS, 29.55 mg of succinic acid and 17.0 mg of sodium hydroxide 1 mL, filtered through a 0.22 μm filter membrane, added to a 10 mL sterile vial, freeze-dried the mixture, sealed and capped to obtain 1 vial that can be used for 99m Tc-labeled lyophilized kit.

[0097] (2) Kit preparation of HpFAPi

[0098] Weigh 1 mg of HpFAPi and dissolve it in 1 mL of 75% ethanol in water at a concentration of 1 μg / μL; then prepare a mixture containing 25 μg (25 μL) HFAPi, 2.0 mg Tricine, 3.0 mg TPPTS, 29.55 mg succinic acid and 17.0 mg sodium hydroxide 1mL of liquid, filtered through a 0.22μm filter membrane, added to a 10mL sterile vial, freeze-dried the mixture, sealed and c...

Embodiment 399

[0099] Example 3 99m Tc-HFAPi and 99m Preparation and quality control of Tc-HpFAPi

[0100] The radiochemical purity (RCP) of the label was determined using HPLC (equipped with a Raytest Gabistar radioactivity detector and an Agilent-35900E digital-to-analog converter) and a YMC-Pack ODS-A C18 analytical column (250 × 4.6 mml.D.S. -5 μm, 12 nm), gradient elution for 20 minutes, flow rate 1 mL / min, wherein mobile phase A is deionized water (containing 0.05% TFA), and mobile phase B is acetonitrile (containing 0.05% TFA). The elution gradient was set to 90% A and 10% B at the beginning, 60% A and 40% B at 17.5 min, and 90% A and 10% B at 20 min.

[0101] (1) 99m Preparation of Tc-HFAPi:

[0102] Add 1 mL Na using a sterile syringe to the HFAPi lyophilization kit (without opening the cap) 99m TcO 4The solution (~740MBq) was reacted in a water bath at 99°C for 15 minutes. After the reaction was completed, the kit was taken out and cooled to room temperature to obtain a radio...

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Abstract

A FAP-α-specific tumor diagnosis SPECT imaging agent, the imaging agent is a small molecule FAP-α inhibitor with a modified N-4-quinolyl-glycine-(2S)-cyanoproline skeleton as a precursor compound, with 99m Tc is a radionuclide, formed with N-tris(hydroxymethyl)methylglycine (Tricine) and triphenylphosphine triisosulfonic acid sodium salt (TPPTS) as cooperative ligands. Compared with the prior art, the imaging agent shows more excellent in vivo biodistribution, higher tumor uptake and tumor / organ uptake ratio, more stable coordination, and then shows excellent in vivo, External stability, due to the characteristics of the coordination structure of the imaging agent of the present invention, the one-step labeling method kit technology can be used, so it has better druggability and is suitable for industrial production and clinical promotion.

Description

technical field [0001] The invention relates to a radionuclide-labeled diagnostic drug complex, including a precursor compound for preparing the complex and a pharmaceutical composition or a drug-forming kit, in particular to a broad-spectrum tumor SPECT targeting FAP-α imaging agent. Background technique [0002] Metastasis accounts for 90% of deaths in patients with malignant tumors, but preventive or therapeutic strategies for tumor metastasis are still lacking. [0003] Tumor is a complex composed of tumor cells and surrounding stromal cells and acellular components. The occurrence and development of tumor is a dynamic process in which tumor cells and their microenvironment promote and co-evolve. The tumor microenvironment includes cells and extracellular matrix, and the formed components are mainly cellular components, including immune cells, endothelial cells, and fibroblasts. The main stromal cells account for about 50% of the total number of tumor cells. CAFs play...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K51/04A61K103/10
CPCA61K51/0482
Inventor 贾兵王凡杨广杰高瀚男李小达史继云马庆杰高识
Owner 嘉兴法伯新天医药科技有限公司