Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Gallium 68 labeled affinity protein PET imaging agent and application thereof

A technology of PET imaging agent and affimer, which is applied in the direction of in vivo radioactive preparations, radioactive carriers, preparations for in vivo experiments, etc., and can solve problems such as insufficient stability

Active Publication Date: 2021-06-01
WEST CHINA HOSPITAL SICHUAN UNIV
View PDF3 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] existing at the same time 68 In the Ga-PDGFR-β target affimer report, monomeric and dimeric affimer molecules were used, and the affinity constant of the monomeric affimer and PDGFR-β was about 249.2nM; while the dimeric affimer had a better affinity constant (32.6nM), and because its dimeric structure depends on the disulfide bond between two monomers, the structure is not stable enough in vivo

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Gallium 68 labeled affinity protein PET imaging agent and application thereof
  • Gallium 68 labeled affinity protein PET imaging agent and application thereof
  • Gallium 68 labeled affinity protein PET imaging agent and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030]Preparation of PDGFR-β Targeted Trimolysin (Z-Tri)

[0031]1.1 Sequence of affinity Z-TRI

[0032]The amino acid sequence of the affinity Z-Tri protein is shown in SEQ ID NO.1.

[0033]1.2 Preparation of the expression plasmid of affinity Z-TRI gene

[0034]The expression plasmid of affinity Z-Tri was constructed by the laboratory pre-design, stored in TOP10 strains (TOP10-PQE30-Z-TRI). Top10-PQE30-Z-Tri hydrochloride was inoculated in a liquid medium containing ampicillin (AMP, 100 μg / ml) LB liquid medium, 37 ° C, 220 rpm shocking overnight, to the bacterial liquid A600To 1. Take some bacterial liquid to extract PQE30-Z-Tri plasmid according to the plasmid extraction kit specification, and the agarose gel electrophoresis is extracted to extract the size of the plasmid, and the company sequencing verifies whether it is PQE30-Z-Tri, which will verify the correct PQE30- The Z-Tri plasmid was stored at 20 ° C.

[0035]1.3 Construction of expression strains Mi5-PQE30-Z-TRI

[0036]The sequence ve...

Embodiment 2

[0054]68Preparation of GA-Z-TRI

[0055]image 3 Shows68A schematic of the GA-Z-Tri affinity probe, where the leftmostmost side is the three polymer probe of the present invention68GA-Z-TRI, its preparation method is as follows:

[0056]3.1Z-TRI and double function chelating agent

[0057]Z-Tri protein 0.5 mg is dissolved in 50 mM sodium hydrogencarbonate solution (pH 8.2 ~ 8.5), with double functional coingent 2 - [(4-isothi cyanophenyl) methyl] -1, 4, 7, 10 - Tetrazo heterocyclic dodecane-1,4,7,10-tetracetic acid (P-SCN-BN-DOTA, referred to as DOTA, after the same) 20 μl (5 moll) was mixed, 37 ° C was incubated at 37 ° C for 2 hours. Using GE PD-10DESALTING Column desalination column, the sodium acetate solution (pH 8.8 ~ 9.0) is a mobile phase, and after removing the unbound DOTA, the successful coupled DOTA-Z-Tri protein is stored in 0.5 m. Sodium acetate (pH 8.8 ~ 9.0) spare.

[0058]3.2Z-Tri68GA tag

[0059]Wash the GE-GA generator using 0.1M super pure hydrochloride68GA CL3The flux, DOTA-Z-T...

Embodiment 3

[0062]68GA-Z-TRI PET imaging effectiveness test

[0063]1) use68GA-Z-Tri bobbin performs PET imaging of subcutaneous humen nude mice to verify its effectiveness.

[0064]The subcutaneous tumor cell line was constructed by subcutaneous tumor cell line, and the malignant glymiloma U-87mg, colon cancer LS-174T, lung cancer A549, osteosarcoma Saos2, breast cancer MDA-MB-231, Hepatic cancer huh7 total 6 malignant tumor skin lower tumor nude mice model.

[0065]After the tumor has a tumor diameter, PET imaging is performed. The specific steps are: 3.7 Mbq of 3.7 Mbq by tail veins from the nude mice after tumor68The Ga-Z-Tri complex protein solution (about 1.5 μg) was developed using MicroPET-CT after 1 hour.Figure 5 As shown, the arrow refers to a tumor, which clearly sees most of the drug through the kidney-bladder pathway to the body, and the corresponding subcutaneous tumor site has obvious radioactive intake, confirmed 68GA-Z-TRI Pixin can be used for tumor PET imaging.

[0066]2) use68Ga-Z-Tri a...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a gallium 68 labeled affinity protein PET (positron emission tomography) developer and the application thereof. The gallium 68 labeled affinity protein PET developer comprises 68Ga-Z-tri, the 68Ga-Z-tri is obtained by labeling affinity protein with gallium 68, the affinity protein comprises PDGFR-beta targeted trimerization affinity protein Z-tri, and the amino acid sequence table of the affinity Z-tri protein is shown as SEQ ID NO.1. According to the invention, a trimeric PDGFR-beta targeting affibody with a unique amino acid sequence is utilized. Compared with a monomer and a dimer affinity, the trimer PDGFR-beta targeting affinity with a unique amino acid sequence has the characteristics of high affinity and high stability, the labeling rate of nuclide can be greatly improved, and the effectiveness of the trimer PDGFR-beta targeting affinity as a PET imaging probe is realized.

Description

Technical field[0001]The present invention relates to the field of nuclear medicine PET developing agents, and more particularly to a gallium 68-labeled complex PET developer and applications.Background technique[0002]Positron Emission Tomography, PET) is a class of fluorine 18 (18F), gallium 68 (68Ga), copper 64 (64Cu), radioactive positive electronic mens, imaging technology, non-invasive diagnosis, using a positive electronic melody with PET probes constructed from different target molecular imaging agents, can accomplish specificity for different diseases, different organs Functional imaging, is important in malignant tumors, neuropsy, cardiovascular and cerebrovascular diseases.[0003]Platelet Derived Growth Factor Receptor-beta, PDGFR-β is an important new blood vessel growth factor receptor, which has a significant difference in diseases with vascular abnormalities in tumors, equipment-based fibrosis. Sexual high expression characteristics. Diagnosis and treatment for the abov...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K51/08A61K51/04
CPCA61K51/08A61K51/0482A61K51/1093C07K16/2863C07K2318/20A61K2039/505A61K51/1057C07K2317/31
Inventor 蔡华伟卢晓风杨浩李林田蓉程惊秋
Owner WEST CHINA HOSPITAL SICHUAN UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com