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<18>F-labeled polypeptide compound, and preparation method and application thereof

A peptide compound, 18F technology, applied in the field of 18F-labeled peptide compound and its preparation, can solve the problems of less imaging probes, long reaction time, low reaction product yield and the like

Active Publication Date: 2016-10-05
SHANGHAI INST OF APPLIED PHYSICS - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are few reports on PET probes based on this target at home and abroad, which makes this invention very innovative and has good application value.
[0007] The existing reports on the CA IX targets targeted by the fluorine-18 labeling technology 18 There are almost no F-labeled polypeptides, and there are very few imaging probes for this target, and the reported methods for labeling nucleic acids are not ideal. The main problem is that the yield of reaction products is low, and the reaction time Very long (Mercier F, Paris J, Kaisin G et al Bioconjugate Chem.2011, 22, 108–114 General Method for Labeling siRNA by Click Chemistry with Fluorine-18 for the Purpose of PET Imaging; Inkster JA, Adam MJ, Storr T et al Nucleosides Nucleotides Nucleic Acids.2009Nov; 28(11):1131-43Labeling of an antisense oligonucleotide with[(18)F]FPy5yne), and existing literature reports 125 The I-labeled compound similar to the structure of the product of the present invention was incubated in serum for 1.5 hours with 50% decomposition (Askoxylakis V, Garcia-Boy R, Rana S, et al.A new peptide ligand fortargeting human carbonic anhydrase IX, identified through the phage displaytechnology[J].PLoS One,2010,5:e15962.), so there is still a lack of a method in this field that can efficiently and stably label polypeptides with fluorine-18

Method used

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  • &lt;18&gt;F-labeled polypeptide compound, and preparation method and application thereof
  • &lt;18&gt;F-labeled polypeptide compound, and preparation method and application thereof
  • &lt;18&gt;F-labeled polypeptide compound, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0072] 20mCi 18 f - By quaternary ammonium type anion column QMA (the product of American Waters company, 18 f - Provided by Shanghai Kexing Pharmaceutical Co., Ltd.) after capture, take 1.0mL K2.2.2 (ie Kryptofix 222) solution (14.4mg K2.2.2, 3.0mg K 2 CO 3 , 960μL acetonitrile, 40μL water solution) will 18 f - Rinse into the reaction bottle, immerse the reaction bottle in an oil bath at 95°C, blow dry with nitrogen, then add 500 μL of anhydrous acetonitrile to dry, repeat the above operation twice.

Embodiment 2

[0074] (1) 30mCi 18 f - By quaternary ammonium type anion column QMA (the product of American Waters company, 18 f - Provided by Kexing Pharmaceutical Co., Ltd.) after capture, take 1.2mL K 222 (i.e. Kryptofix 222) solution (17.5mg K 222 , 3.5 mg K 2 CO 3 , 1152μL acetonitrile, 48μL water solution) will 18 Rinse F into the reaction bottle, immerse the reaction bottle in an oil bath at 95°C, dry it with nitrogen, then add 500 μL of anhydrous acetonitrile to dry it, repeat the drying with anhydrous acetonitrile twice;

[0075] (2) 500 μL of anhydrous acetonitrile solution containing 5 mg 2-azidoethyl p-toluenesulfonate was rapidly added to the solution containing K 222 、K 2 CO 3 and 18 f - In the mixture, stop the reaction after closed reaction at 95°C for 10 minutes, and cool in an ice-water bath to obtain compound B1, the labeling rate can reach more than 97%;

[0076]

[0077] (3) Add 200 μL of acetonitrile to the reaction liquid containing compound B1, nitroge...

Embodiment 3

[0082] (1) Add 500 μL of anhydrous acetonitrile solution containing 5 mg of 2-azidoethyl p-toluenesulfonate rapidly to the solution containing K 222 、K 2 CO 3 and 18 f - In the mixture, stop the reaction after closed reaction at 95°C for 10 minutes, and cool in an ice-water bath to obtain compound B1, the labeling rate can reach more than 97%;

[0083]

[0084] (2) Add 200 μL of acetonitrile to the reaction solution containing compound B1, carry out nitrogen gas auxiliary flow, carry out distillation, and collect the condensate, distill for 10-20min to obtain about 700 μL of acetonitrile condensate collection liquid containing purified compound B1, the distillation efficiency Can reach 75%;

[0085] (3) Add 40 μL of 0.45 mol / L copper sulfate solution and 40 μL of 1.5 mol / L sodium ascorbate solution successively into a 1.5 mL finger tube, mix well and add 350 μL of PBS solution containing 2.0 mg of compound D2 (pH = 6.0), after vortex mixing for 1 min, 300 μL of acetoni...

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Abstract

The invention discloses a <18>F-labeled polypeptide compound with a structure represented by a formula 1. R1 is as shown in the formulas. R2 is C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C5-C7 cycloalkyl, polyethylene glycol, C6-C10 aryl, C6-C10 aryl-C1-C4 alkyl or C1-C4 alkyl-C6-C10 aryl-C1-C4 alkyl. The invention also provides a preparation method of the <18>F-labeled polypeptide compound. The method comprises the following steps: in a solvent, under Cu(I) catalysis, a compound D and a compound B are subjected to nitrine and terminal alkynyl 1,3-dipolar cycloaddition reaction. The invention also provides an application of the <18>F-labeled polypeptide compound. The <18>F-labeled polypeptide compound has the advantages of high imaging resolution and good stability. According to the preparation method of the <18>F-labeled polypeptide compound, the radiochemical yield is substantially improved compared to that of prior arts.

Description

technical field [0001] The present invention relates to the field of polypeptide compounds, in particular to a 18 F-labeled polypeptide compound and its preparation method and application. Background technique [0002] Carbonic anhydrase IX (CA IX) is one of the isomers of the carbonic anhydrase family. It is a zinc-containing metalloenzyme involved in many physiological processes in the body, such as acid-base balance, ion transport, gas exchange, calcification, etc. ( Claudiu T. Drug Design of Zinc-Enzyme Inhibitors [M]. Wiley, 2009. Simone G.D. BBA-PROTEINS PROTEOM, 2010: 404-409.). [0003] Studies have found that CA IX is a new type of tumor-associated antigen, which can be used as a tumor cell-specific biomarker. At the same time, CA IX is closely related to tumor hypoxia. As a marker of tumor hypoxia, it plays a role in regulating cell Potential role in proliferation and tumorigenesis. Due to the imbalance of blood supply and demand in the local tumor or the vigoro...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06C07K7/08C07K1/13A61K51/08A61K101/02
Inventor 张岚贾丽娜
Owner SHANGHAI INST OF APPLIED PHYSICS - CHINESE ACAD OF SCI
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