A D-type polypeptide radiopharmaceutical targeting HER2 and its preparation method

A technology of radiopharmaceuticals and radionuclides, which is applied in the field of new tumor diagnostic radiopharmaceuticals, can solve problems such as poor stability in the body and affect the diagnosis effect, and achieve the effects of improving intake, good diagnosis and treatment effect, and improving metabolic stability in the body

Active Publication Date: 2020-02-18
PEKING UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, H6 polypeptide still has problems such as low tumor uptake, poor stability in vivo, and obvious gallbladder uptake, which affect the diagnostic effect

Method used

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  • A D-type polypeptide radiopharmaceutical targeting HER2 and its preparation method
  • A D-type polypeptide radiopharmaceutical targeting HER2 and its preparation method
  • A D-type polypeptide radiopharmaceutical targeting HER2 and its preparation method

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Experimental program
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Effect test

Embodiment 99

[0055] This embodiment takes 99m Tc-HYNIC-PEG 4 -ref Polypeptide radiopharmaceutical and its preparation method as an example.

[0056] 99m Tc-HYNIC-PEG 4 In -ref, the ref polypeptide is a D-type amino acid linear polypeptide (sequence: Arg-Glu-Phe-Val-Phe-Phe-Leu-Tyr), radionuclide 99m Tc labels the ref polypeptide with a bifunctional chelating agent HYNIC, and a polyethylene glycol molecule (PEG) with a degree of polymerization of 4 pharmacokinetic modification molecules is also connected between the ref polypeptide and the bifunctional chelating agent. 4 ), the ref polypeptide radiopharmaceutical is 99m Tc-HYNIC-PEG 4 -ref (short for 99m Tc-HP 4 -ref), the ref polypeptide radiopharmaceutical is a colorless transparent liquid injection. Structural diagram such as figure 1 .

[0057] 99m Tc-HYNIC-PEG 4 -ref is prepared as follows:

[0058] HYNIC-PEG 4 Preparation of -COOH: Fmoc-protected PEG 4-COOH was dissolved in DMF, and piperidine was added to make the fina...

Embodiment 2

[0067] HYNIC-ref: Dissolve the ref polypeptide and HYNIC-NHS in DMF, add DIEA to adjust the pH value to 8.5-9.0, stir overnight at room temperature, add 50% ACN aqueous solution to the reaction solution and filter, and the filtrate is passed through YMC-Pack ODS- A semi-preparative column HPLC separation and purification. The HPLC method was a YMC-Pack ODS-AC18 semi-preparative column (250×10 mml.D. S-5 μm, 12 nm) prepared by Agilent 1260 Infinity HPLC equipment, with a gradient elution time of 30 min and a flow rate of 4 mL / min , the mobile phase A was deionized water (containing 0.05% TFA), and the mobile phase B was acetonitrile (containing 0.05% TFA). The elution gradient was: 100% A and 0% B at start, 28% A and 72% B at 18 minutes, 100% A and 0% B at 30 minutes. The fractions of the target were collected, the collected liquid was combined and lyophilized, and the obtained product was analyzed by MALDI-TOF-MS mass spectrometry m / z=1423.41 ([M+H] + ), confirmed as the exp...

Embodiment 3

[0071] DOTA-ref: Dissolve the ref polypeptide and DOTA-NHS in DMF, add DIEA to adjust the pH value to 8.5-9.0, stir overnight at room temperature, add 50% ACN aqueous solution to the reaction solution and filter, and the filtrate is passed through YMC-Pack ODS- A semi-preparative column HPLC separation and purification. The HPLC method uses an Agilent 1260 HPLC system equipped with a YMC-Pack ODS-A semi-preparative column (250×10 mml.D. S-5 μm, 12 nm), gradient elution for 20 minutes, and a flow rate of 4 mL / min, where flow A The phase was deionized water (with 0.05% TFA), and the mobile phase B was acetonitrile (with 0.05% TFA). The elution gradient was set to 90% A and 10% B at the beginning, 40% A and 60% B at 20 minutes. The fractions of the target were collected, the collected liquid was combined and lyophilized, and the product obtained was analyzed by MALDI-TOF-MS mass spectrometry m / z=1506.72 ([M+H] + ), confirmed as the expected product DOTA-ref.

[0072] 68 Ga-DO...

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Abstract

The invention discloses a D-type polypeptide radiopharmaceutical of target HER2 and a preparation method. The radiopharmaceutical is prepared from D-type amino acid linear polypeptide and radionuclide, radionuclide marks D-type amino acid linear polypeptide through a chelating agent, and the sequence of D-type amino acid linear polypeptide is Arg-Glu-Phe-Val-Phe-Phe-Leu-Tyr. Radionuclide in the radiopharmaceutical in vivo is concentrated to the tumor part through D-type amino acid linear polypeptide, and HER2 positive tumor is subjected to imaging diagnosis by utilizing the single photon emission computed tomography technique of nuclear medicine.

Description

technical field [0001] The present invention relates to a novel radiopharmaceutical for tumor diagnosis, which can specifically target HER2-positive tumors, and particularly relates to imaging diagnosis for patients with HER2-positive tumors, as well as medication guidance and real-time curative effect monitoring for patients treated with the anticancer drug Herceptin . Background technique [0002] In my country, the incidence and death toll of cancer are increasing year by year. Among women, the morbidity and mortality of breast cancer remain high. In 142 countries around the world, breast cancer is the most common cancer among women. According to statistics, the survival rate of early diagnosis of tumors is much higher than that of late diagnosis, especially the cure rate of early diagnosis of breast cancer is extremely high, so early detection and early treatment is an important means to overcome cancer. However, the symptoms of many tumors are not obvious in the early...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K51/08A61K103/10A61K103/00
CPCA61K51/08
Inventor 王凡史继云杜帅樊贾兵高瀚男罗麒罗创维
Owner PEKING UNIV
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