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Preparation method of Cu-64 labeled Dimer-San A cyclic peptide derivative pancreatic cancer molecular probe

A technology of molecular probes and derivatives, applied in peptides, drug combinations, digestive system, etc., can solve the problems of misdiagnosis and missed diagnosis of benign and malignant tumors, obvious differences in anti-tumor activity, etc., and achieve simple labeling methods and good imaging effects , High stability effect

Active Publication Date: 2018-02-09
李玉民 +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

18 As a non-specific tumor imaging agent, F-FDG PET / CT has obvious shortcomings in the differential diagnosis of benign and malignant tumors in the early stage: false positives and false negatives coexist, resulting in misdiagnosis and missed diagnosis of benign and malignant tumors
[0009] So far, more than 100 kinds of San A cyclic peptide derivatives have been synthesized, and their antitumor activities are significantly different.

Method used

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  • Preparation method of Cu-64 labeled Dimer-San A cyclic peptide derivative pancreatic cancer molecular probe
  • Preparation method of Cu-64 labeled Dimer-San A cyclic peptide derivative pancreatic cancer molecular probe
  • Preparation method of Cu-64 labeled Dimer-San A cyclic peptide derivative pancreatic cancer molecular probe

Examples

Experimental program
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Effect test

Embodiment 1

[0052] Example 1 The preparation method of Cu-64-labeled Dimer-San A cyclic peptide derivative pancreatic cancer molecular probe comprises the following steps:

[0053] (1) Dissolve NOTA-Dimer-Sansalvamide A in acetonitrile to prepare a peptide solution with a concentration of 1 μg / μL.

[0054] ⑵ at 37 MBq 64 CuCl 2 Add 300 μL of 0.1 M ammonium acetate (NH 4 OAc) buffer to react to obtain the reaction solution 64 Cu(OAc) 2 .

[0055] (3) Add 5 μg of peptide solution to the reaction solution 64 Cu(OAc) 2 , heated at 45°C for 45 min, and kept shaking during the heating process to obtain the product 64 Cu-NOTA-Dimer-Sansalvamide A, referred to as 64 Cu-NOTA-Dimer-San. After HPLC (high performance liquid chromatography) analysis and separation and purification, the labeling rate is >97%, and its structural formula is as follows:

[0056] .

[0057] ⑷ product 64 Cu-NOTA-Dimer-San was removed with a suspension dryer at 40°C, dissolved in phosphate buffered saline (PBS)...

Embodiment 2

[0059] Example 2 The preparation method of Cu-64-labeled Dimer-San A cyclic peptide derivative pancreatic cancer molecular probe comprises the following steps:

[0060] (1) Dissolve NOTA-Dimer-Sansalvamide A in acetonitrile to prepare a peptide solution with a concentration of 1 μg / μL.

[0061] ⑵ at 111 MBq 64 CuCl 2 Add 300 μL of 0.1 M ammonium acetate (NH 4 OAc) buffer to react to obtain the reaction solution 64 Cu(OAc) 2 .

[0062] (3) Add 10 μg of peptide solution to the reaction solution 64 Cu(OAc) 2 , heated at 45°C for 45 min, and kept shaking during the heating process to obtain the product 64 Cu-NOTA-Dimer-Sansalvamide A, referred to as 64 Cu-NOTA-Dimer-San. After HPLC (high performance liquid chromatography) analysis and separation and purification, the labeling rate was >97%, and its structural formula was the same as in Example 1.

[0063] ⑷ product 64Cu-NOTA-Dimer-San was removed with a suspension dryer at 40°C, dissolved in phosphate buffered saline (P...

Embodiment 3

[0065] Example 3 The preparation method of Cu-64-labeled Dimer-San A cyclic peptide derivative pancreatic cancer molecular probe includes the following steps:

[0066] (1) Dissolve NOTA-Dimer-Sansalvamide A in acetonitrile to prepare a peptide solution with a concentration of 1 μg / μL.

[0067] ⑵ at 74 MBq 64 CuCl 2 Add 300 μL of 0.1 M ammonium acetate (NH 4 OAc) buffer to react to obtain the reaction solution 64 Cu(OAc) 2 .

[0068] (3) Add 8 μg of peptide solution to the reaction solution 64 Cu(OAc) 2 , heated at 45°C for 45 min, and kept shaking during the heating process to obtain the product 64 Cu-NOTA-Dimer-Sansalvamide A, referred to as 64 Cu-NOTA-Dimer-San. After HPLC (high performance liquid chromatography) analysis and separation and purification, the labeling rate was >97%, and its structural formula was the same as in Example 1.

[0069] ⑷ product 64 Cu-NOTA-Dimer-San was removed with a suspension dryer at 40°C, dissolved in phosphate buffered saline (PBS...

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Abstract

The invention relates to a preparation method of a Cu-64 labeled Dimer-San A cyclic peptide derivative pancreatic cancer molecular probe. The method comprises the following steps: (1) dissolving NOTA-Dimer-Sansalvamide A in acetonitrile to prepare a polypeptide solution having a concentration of 1[mu]g / [mu]L; (2) adding an ammonium acetate buffer solution into <64>CuCl2, and performing a reactionto obtain a reaction solution <64>Cu(OAc)2; (3) adding the polypeptide solution into the reaction solution <64>Cu(OAc)2, performing heating, and performing continuous shaking in the heating process toobtain a product <64>Cu-NOTA-Dimer-Sansalvamide A; and (4) dissolving the product <64>Cu-NOTA-Dimer-San with a phosphate buffer solution, and performing filtration through a filter membrane to obtainthe <64>Cu labeled Dimer-Sansalvamide A cyclic peptide derivative pancreatic cancer molecular probe. The invention provides the <64>Cu labeled NOTA-Dimer-San novel developer by taking the NOTA-Dimer-San molecule as a <64>Cu labeled precursor and Hsp90 as a target spot for tumor development for the first time; and the developer has the potential advantage of tumor specificity in clinical application.

Description

technical field [0001] The invention relates to a method for preparing a probe, in particular to a method for preparing a Cu-64-labeled Dimer-San A ring peptide derivative pancreatic cancer molecular probe. Background technique [0002] Pancreatic cancer is the fifth most malignant tumor in the world. The median survival time is less than 6 months, and the overall 5-year survival rate is less than 6%. Only 10% of patients are suitable for surgical treatment. The poor prognosis is related to the lack of early diagnosis of the disease. closely related. With the aging of our population, the incidence of pancreatic cancer in our country has increased, and it will become a major health problem in our country in the next few years. [0003] At present, the routine imaging diagnosis of pancreatic cancer includes ultrasound (including endoscopic ultrasound), CT and MRI. However, these structural images have poor specificity for the diagnosis of pancreatic cancer. Imaging medicine ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/64A61K51/08A61P1/08A61P35/00A61K103/00
CPCA61K51/08C07K7/64
Inventor 李玉民陈凯王晓慧
Owner 李玉民
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