Radioisotope labeled polypeptide developer of targeted transferrin receptor and application of radioisotope labeled polypeptide developer

A technology of radioisotopes and transferrin, which is applied in the field of radioisotope-labeled polypeptide imaging agents, can solve the problems of long distribution time, short elimination half-life, and functional inactivation, achieving high accuracy and sensitivity, simple labeling methods, and labeling high rate effect

Pending Publication Date: 2020-12-08
SUN YAT SEN UNIV CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Existing studies are mostly based on the TFRC-Tf mechanism, using TF as a targeting ligand to design imaging agents. However, there are three shortcomings in this mechanism: ① Endogenous Tf in the body can compete with Tf ligand imaging agents for TFRC ②Tf protein has a large molecular weight (76-81kDa), and the distribution in the body takes a long time, requiring a radioactive isotope with a particularly

Method used

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  • Radioisotope labeled polypeptide developer of targeted transferrin receptor and application of radioisotope labeled polypeptide developer
  • Radioisotope labeled polypeptide developer of targeted transferrin receptor and application of radioisotope labeled polypeptide developer
  • Radioisotope labeled polypeptide developer of targeted transferrin receptor and application of radioisotope labeled polypeptide developer

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preparation example Construction

[0093] Preparation of polypeptide precursors

[0094] 1. Preparation of Fmoc-Pip-OH

[0095] Fmoc-Pip-OH can be obtained by protecting 4-amino-(1-carboxymethyl)piperidine with tert-butanol and Fmoc-Cl, of course, it can also be prepared by other methods familiar to those skilled in the art.

[0096] The structural formula of Fmoc-Pip-OH finally prepared in this embodiment is as follows:

[0097]

[0098] 2. Preparation of Fmoc-AEEP-OH

[0099] Fmoc-AEEP-OH can be obtained by sequential protection of 3-[2-(2-aminoethoxy)ethoxy]-propionic acid through tert-butanol and Fmoc-Cl. Of course, other methods familiar to those skilled in the art can also be used. method to prepare.

[0100] The structural formula of Fmoc-AEEP-OH finally prepared in this embodiment is as follows:

[0101]

[0102] 3. Preparation of NOTA-tBu(2)

[0103] NOTA-tBu (2) can be prepared by reacting NOTA and tert-butanol under the trifluoromethanesulfonic anhydride catalyzed system, and can also be p...

Embodiment 168

[0121] Example 1 68 Preparation of Ga-NOTA-Pip-HAIYPRH

[0122] 1. 68 Ga-labeled NOTA-Pip-HAIYPRH

[0123] Dissolve 20ug of the above-mentioned polypeptide precursor NOTA-Pip-HAIYPRH in 200ul 1M sodium acetate solution, put it into a reaction bottle, and draw 0.05mol / L HCl 5ml with a 5ml syringe to 68 Ge / 68 The Ga generator performs segmental leaching, the flow rate is 1ml / min, and the middle 1.5ml of high activity is collected 68 Add the Ga eluent into the reaction bottle, adjust the pH of the reaction solution to 3.8-4.2, seal it, and place it in a water bath with a multifunctional heater at 90°C for 10 minutes.

[0124] The radiochemical purity of the product was measured, and if the radiochemical purity of the product was ≥80%, it indicated that the labeling was successful.

[0125] 2. Product purification

[0126] Draw the above-mentioned labeled product solution after the reaction with a syringe, add it to the activated Sep-pak C-18 column, and then use 5ml physio...

Embodiment 268G

[0131] Example 2 68 Preparation of Ga-NOTA-AEEP-HAIYPRH

[0132] 1. 68 Ga-labeled NOTA-AEEP-HAIYPRH

[0133] Dissolve 20ug of the above-mentioned polypeptide precursor NOTA-AEEP-HAIYPRH in 200ul 1M sodium acetate solution, put it into a reaction bottle, and draw 0.05mol / L HCl 5ml with a 5ml syringe to 68 Ge / 68 The Ga generator performs segmental leaching, the flow rate is 1ml / min, and the middle 1.5ml of high activity is collected 68 Add the Ga eluent into the reaction bottle, adjust the pH of the reaction solution to 3.8-4.2, seal it, and place it in a water bath with a multifunctional heater at 90°C for 10 minutes.

[0134] The radiochemical purity of the product was measured, and if the radiochemical purity of the product was ≥80%, it indicated that the labeling was successful.

[0135] 2. Product purification

[0136] Draw the above-mentioned labeled product solution after the reaction with a syringe, add it to the activated Sep-pak C-18 column, and then use 5ml phy...

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Abstract

The invention discloses a radioisotope labeled polypeptide developer of a targeted transferrin receptor and application of the radioisotope labeled polypeptide developer. The invention particularly discloses a 68Ga chelation reaction labeling method of two polypeptide precursors and application of the two polypeptide precursors as an imaging agent in positron emission tomography (PET) of a transferrin receptor overexpressed tumor. The radioisotope labeled product has radiochemical purity of more than 95% and good in-vivo stability, can be rapidly aggregated within 5 minutes at a tumor site, has obvious tumor muscle contrast, can realize clear imaging of tumor tissues and margins, and has a certain difference between pharmacokinetics and biodistribution due to structural modification of different linking groups, so that the compound can be used as a tumor-specific imaging agent of a targeted transferrin receptor.

Description

technical field [0001] The invention belongs to the field of preparation and application of biomedical imaging agents, and in particular relates to radioisotope-labeled polypeptide imaging agents targeting transferrin receptors and applications thereof. Background technique [0002] Positron Emission Tomography (PET) is the most cutting-edge medical molecular imaging technology, widely used in the early diagnosis and curative effect evaluation of malignant tumors, cardiovascular, nervous system and other major diseases. PET has significant advantages: ① three-dimensional functional imaging of radioactive probes can be obtained, showing the spatial distribution of biomolecular activities in human models; ② non-invasive in vivo imaging can realize real-time visualization of cancer-related processes, and promote the understanding of tumor evolution; ③By combining with other imaging modalities such as magnetic resonance imaging (MRI) and computed tomography (CT) to form multimod...

Claims

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Application Information

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IPC IPC(8): A61K51/08C07K7/06A61K103/00
CPCA61K51/08C07K7/06
Inventor 樊卫王瑞敏张晓飞张旭
Owner SUN YAT SEN UNIV CANCER CENT
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