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<188>Re-labeled tumor-targeted disulfide bond RGD cyclic peptide molecular probe and preparation method thereof

A tumor targeting and molecular probe technology, applied in the field of molecular imaging, can solve the problems of reduced biological activity of polypeptides and improper methods, and achieve the effect of maintaining stability, significant effect, and increasing tumor uptake

Active Publication Date: 2018-10-16
WUXI MATERNAL & CHILD HEALTH HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] At present, the common disulfide bond ring-forming target polypeptide labeling is often used as a direct method, while some labeling by indirect methods is due to improper methods, bifunctional chelating linkers and disulfide bonds can compete for binding 188 Re, both cause the reduction of the biological activity of the peptide

Method used

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  • &lt;188&gt;Re-labeled tumor-targeted disulfide bond RGD cyclic peptide molecular probe and preparation method thereof
  • &lt;188&gt;Re-labeled tumor-targeted disulfide bond RGD cyclic peptide molecular probe and preparation method thereof
  • &lt;188&gt;Re-labeled tumor-targeted disulfide bond RGD cyclic peptide molecular probe and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1188

[0026] Example 1 188 Preparation of Re-HYNIC-c(CRGDfkC) Molecular Probe

[0027] at 200μCi 188 ReO 4 - Fill the solution with nitrogen to prevent oxidation, then add 2mg of CuCl as a reducing agent, then add 2mg of sodium gluconate, adjust the pH of the reaction system to 6.0 with dilute hydrochloric acid, and react at 20°C for 90min. Then add an appropriate amount of Na to the reaction solution 2 S 2 o 3 , the pre-restored 188 After the color of the Re reaction solution was adjusted to blue-green, 100 μg of HYNIC-c (CRGDfkC) was added and reacted at 25° C. for 90 minutes. The amino acid sequence of CRGDfkC is shown in SEQ ID NO.1.

Embodiment 2188

[0028] Example 2 188 Preparation of Re-HYNIC-c(CRGDfkC) Molecular Probe

[0029] at 200μCi 188 ReO 4 - Fill the solution with nitrogen to prevent oxidation, then add 2mg of CuCl as a reducing agent, then add 5mg of sodium gluconate, adjust the pH of the reaction system to 5.8 with dilute hydrochloric acid, and react at 55°C for 60min. Then add an appropriate amount of Na to the reaction solution 2 S 2 o 3 , the pre-restored 188 After the color of the Re reaction solution was adjusted to blue-green, 150 μg of HYNIC-c (CRGDfkC) was added and reacted at 60° C. for 30 minutes. The amino acid sequence of CRGDfkC is shown in SEQ ID NO.1.

Embodiment 3188

[0030] Example 3 188 Preparation of Re-HYNIC-c(CRGDfkC) Molecular Probe

[0031] at 200μCi 188 ReO 4 - Fill the solution with nitrogen to prevent oxidation, then add 1mg of CuCl as a reducing agent, and then add 10mg of sodium gluconate, adjust the pH of the reaction system to 5.5 with dilute hydrochloric acid, and react at 45°C for 70min. Then add an appropriate amount of Na to the reaction solution 2 S2 o 3 , the pre-restored 188 After the color of the Re reaction solution was adjusted to blue-green, 1000 μg of HYNIC-c (CRGDfkC) was added and reacted at 45° C. for 70 minutes. The amino acid sequence of CRGDfkC is shown in SEQ ID NO.1.

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Abstract

The invention discloses a <188>Re-labeled tumor-targeted disulfide bond RGD cyclic peptide molecular probe and a preparation method thereof. The <188>Re-labeled tumor-targeted disulfide bond RGD cyclic peptide molecular probe comprises cyclic peptide RGD and radionuclide <188>Re which are linked through HYNIC. The serum stability of the <188>Re-labeled tumor-targeted disulfide bond RGD cyclic peptide molecule has significant difference from that with a pretinning method, the tumor-bearing nude mouse tumor intake is significantly increased, and the SPECT development effect is significant. <188>Re is reduced with copper chloride, direct action between a strong reducing agent and disulfide bonds is avoided under the weak oxidizing agent after prereduciton, the stability of the cyclic peptidestructure is maintained, reduction of tumor-targeted biological functions due to damage of a direct method to disulfide bonds is effectively avoided, and the in-vivo and in-vitro stability of the disulfide bond RGD cyclic peptide labeled with the method is higher than that with the direct method.

Description

technical field [0001] The invention relates to the technical field of molecular imaging, in particular to a 188 Re-labeled tumor targeting disulfide bond RGD cyclic peptide molecular probe and its preparation method. Background technique [0002] At present, radionuclide-labeled peptides, as a new class of targeted drugs, have been increasingly used in the diagnosis and treatment of tumors, infections, thrombosis and other diseases. Taking advantage of the specificity, selectivity, saturation, strong affinity and obvious biological effects of the combination of receptors and their ligands, the ligands are used as carriers of radionuclides, and through ligand-receptor targeting mediation, increase The concentration of drugs in the local lesion, the improvement of synergistic effect, and the purpose of targeted therapy are currently one of the most active research frontiers. In the development process of such targeted drugs, the selection and modification of polypeptides ar...

Claims

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Application Information

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IPC IPC(8): A61K51/08A61P35/00A61K103/10
CPCA61K51/082A61P35/00
Inventor 陈钰陈萱杨蕊周洁唐秋莎臧嘉陈月娟陈道桢
Owner WUXI MATERNAL & CHILD HEALTH HOSPITAL