Cyclic polypeptide radiopharmaceutical for integrin alpha v beta 6 targeting and preparation method thereof

A technology of radiopharmaceuticals and cyclic polypeptides, which is applied in the direction of radioactive carriers, can solve problems such as instability and poor tumor imaging effects, and achieve the effects of reducing the number of amino acids, increasing in vivo stability, and reducing synthesis costs

Active Publication Date: 2018-12-28
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since RGDLATLRQLAQEDGVVGVRK is a linear polypeptide, it is unstable in vivo, and the tumor imaging effect is not good

Method used

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  • Cyclic polypeptide radiopharmaceutical for integrin alpha v beta 6 targeting and preparation method thereof
  • Cyclic polypeptide radiopharmaceutical for integrin alpha v beta 6 targeting and preparation method thereof
  • Cyclic polypeptide radiopharmaceutical for integrin alpha v beta 6 targeting and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] The cyclic polypeptide radiopharmaceutical for integrin αvβ6 targeting is a radionuclide-bifunctional chelating agent-cyclatide polypeptide, and the radionuclide is labeled with a bifunctional chelating agent for the cycratide polypeptide. The structure of the cycratide polypeptide is shown in formula (1):

[0031]

[0032] The preparation method of this compound:

[0033] Include the following steps:

[0034] a. Preparation of bifunctional chelating agent-cycratide polypeptide: dissolve cycratide polypeptide in alkaline buffer, add bifunctional chelating agent, mix and react at room temperature for 3-10 hours, separate and purify the reaction mixture by chromatography, and collect product peaks The product, freeze-dried to obtain a white powder that is a bifunctional chelating agent-cycratide polypeptide;

[0035] b. Preparation of radionuclide-bifunctional chelating agent-cycratide polypeptide: add radionuclide to the weakly acidic buffer of the bifunctional chelati...

Embodiment 2

[0046] A cyclic polypeptide radiopharmaceutical for integrin αvβ6 targeting, wherein: the bifunctional chelator is DOTA-NHS or p-SCN-Bn-NOTA, and the radionuclide is 68 Ga or 64 The preparation method of Cu, cyclatide polypeptide is as in Example 1.

[0047] Preparation method of cyclic polypeptide radiopharmaceutical for integrin αvβ6 targeting:

[0048] In step a, the bifunctional chelating agent is DOTA-NHS or p-SCN-Bn-NOTA, and the specific operation steps are: take the cycratide polypeptide and dissolve it in 500 μL of 0.1mol / L NaHCO 3 buffer (pH=8.5-9.0), and then add bifunctional chelating agent (dissolved in DMF). After mixing, react at room temperature for 5 h, and then inject the reaction mixture into semi-preparative HPLC for separation and purification. The product peaks were collected, and acetonitrile was removed by rotary evaporation, and then freeze-dried into a white powder by a lyophilizer;

[0049] In step b, the radionuclide is 68 Ga or 64 Cu, the spe...

Embodiment 3

[0054] Cyclic polypeptide radiopharmaceuticals for integrin αvβ6 targeting, wherein: the bifunctional chelator is DOTA or NOTA or derivatives thereof, and the radionuclide is 68 Ga or 64 The preparation method of Cu, cyclatide polypeptide is as in Example 1.

[0055] Preparation method of cyclic polypeptide radiopharmaceutical for integrin αvβ6 targeting:

[0056] In step a, the bifunctional chelating agent is DOTA or NOTA or its derivatives, and the specific operation steps are: after mixing the bifunctional chelating agent with EDC and SNHS in a certain molar ratio, react at 4°C for 0.5-2h to activate. Take the cycratide polypeptide and dissolve it in 500 μL of 0.1mol / L NaHCO 3 buffer solution (pH=8.5-9.0), and then add the activated bifunctional chelating agent. After mixing, react at room temperature for 5 h, and then inject the reaction mixture into semi-preparative HPLC for separation and purification. The product peaks were collected, and acetonitrile was removed by...

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Abstract

The invention discloses a cyclic polypeptide radiopharmaceutical for integrin alpha v beta 6 targeting and a preparation method thereof. The radiopharmaceutical is a radionuclide-bifunctional chelating agent-cycratide polypeptide. The radionuclide labels the cycratide polypeptide by a bifunctional chelating agent, and the cycratide polypeptide is of a cyclic structure composed of 8 amino acids. The radiopharmaceutical achieves specific nuclear medicine positron emission computed tomography (PET) imaging diagnosis for integrin alpha v beta 6 positive tumors or integrin alpha v beta 6 positive lesions (such as wound healing and hepatic pulmonary fibrosis) by means of specific recognition of the integrin alpha v beta 6 by the cycratide polypeptide.

Description

technical field [0001] The present invention relates to the technical field of radiopharmaceuticals for imaging diagnosis of tumors or other lesions, in particular to positron emission computed tomography for targeted nuclear medicine for integrin αvβ6 positive tumors or other lesions (such as wound healing, liver and lung fibrosis, etc.) Cyclized polypeptide radiopharmaceutical for (PET) imaging diagnosis and its preparation method. Background technique [0002] Integrin is a family of cell adhesion receptors. It is a heterodimeric transmembrane glycoprotein formed by two subunits of α and β through non-covalent bonds. It mediates the interaction between cells and extracellular matrix. the most important molecule. So far, 18 kinds of α subunits and 8 kinds of β subunits have been found in mammals, and their combination can form 24 kinds of integrin molecules with different functions. As a member of the integrin family, integrin αvβ6 was found to be highly expressed in man...

Claims

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Application Information

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IPC IPC(8): A61K51/08A61K103/00
Inventor 刘昭飞王凡冯薰杨志李囡
Owner PEKING UNIV
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