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Neovascular-targeting contrast medium composition and method for preparing same

An angiogenesis and contrast agent technology, which can be used in preparations for in vivo experiments, biomaterial analysis, chemical instruments and methods, etc. strength, excellent tissue permeability, and biostability

Active Publication Date: 2021-03-19
KOREA BASIC SCI INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] Currently, although more than 300,000 antibodies have been reported for commercial use, they can only be observed in immobilized cells. For these reasons, it is impossible to observe the contact of proteins or the interaction between proteins in cells in real time.
Also, existing antibodies cannot be used effectively in living cells because they are too large or chemically unstable

Method used

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  • Neovascular-targeting contrast medium composition and method for preparing same
  • Neovascular-targeting contrast medium composition and method for preparing same
  • Neovascular-targeting contrast medium composition and method for preparing same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Example 1. Preparation of contrast agents for targeting angiogenesis

[0057] 2,3,5,6-tetrafluorophenyl-6-[ 18 Fluoro]-flunicotinate (2,3,5,6-tetrafluorophenyl-6-[ 18 F]-fluoronicotinate).

[0058] The 2,3,5,6-tetrafluorophenyl-6-[ 18 Fluoro]-flunicotinate and 0.2ml of 0.1M sodium bicarbonate (NaHCO 3 ) aqueous solution was reacted together at normal temperature for 10 minutes, and after removing unreacted substances using a size exclusion column (size exclusion column) (PD-10 type, GE Healthcare Company), finally prepared 43 mCi 18 Fluoro-Nanobodies.

[0059] Prepared using the Nanobody given by him that contains lysine (Lysine) and hexahistidine tag (His6) in the base sequence 1 18 Fluorine-nanobodies are abbreviated as Nbs-#1 and Nbs-#2, respectively.

[0060] Table 1 shows the results of confirming the radioactivity (radioactivity) of 300 µL aliquots sequentially collected using a PD-10 type column.

[0061] Table 1

[0062] vial Activity (uCi / 30...

experiment example 1

[0063] Experimental example 1. Confirmation of labeling rate of contrast agent for targeting angiogenesis

[0064] Utilize radioactive thin-layer chromatography (Radio-TLC) to confirm that prepared in embodiment 1 18 The radiochemical yield of fluoro-nanobodies, the results of which are as follows figure 1 shown.

[0065] Such as figure 1 As shown, the 2,3,5,6-tetrafluorophenyl-6-[ 18When the fluoro]-flunicotinate and the nanobody react for 10 minutes at normal temperature, the radiochemical yield is over 93%.

experiment example 2

[0066] Experimental example 2. Confirmation of the angiogenesis targeting of the present invention at the tumor site 18 Fluoro-Nanobody Alpha v beta 3 Integrin targeting effects

[0067] In order to confirm the contrast effect of the contrast agent composition of the present invention prepared in the above-mentioned Example 1 in the tumor mouse animal model, the following experiment was carried out.

[0068] Will 18 F-cRGDfk was used as a positive control to confirm that α v beta 3 Integrin targeting effects.

[0069] Specifically, U87-MG cells (U87-MG cells) were xenografted (inoculation) into athymic nude mice (female, 6-8 weeks old) to prepare animal models. When the tumor grows to 0.8cm-1cm in size, inject (1mg / kg) from the tail vein and analyze the contrast effect according to the time. The result is as figure 2 and image 3 shown.

[0070] Such as figure 2 indicated, intravenous infusion 18 F-cRGDfk or 18 After the fluorine-nanobody, one hour later, it wa...

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Abstract

The present invention relates to a neovascular-targeting contrast medium composition and a method for preparing same. The neovascular-targeting contrast medium composition according to the present invention exhibits high binding force to neovascularization-associated [alpha]v[beta]3 integrin, excellent tissue permeability and biostability, enables simple measurement in vitro, in vivo, or ex vivo,and thus is effective in the detection of neovascularization and in diagnosing diseases associated therewith, and therefore can be usefully employed in the relevant industries.

Description

technical field [0001] The present invention relates to contrast agent compositions for targeting angiogenesis and methods for their preparation. Background technique [0002] Positron Emission Tomography (PET) is a device for imaging the distribution of radiopharmaceuticals injected into a living body, which can provide early detection of diseases by imaging biological changes in the human body caused by diseases. Provide accurate information for the determination of diagnosis and treatment methods. Therefore, the importance of nuclear medicine imaging equipment is increasing day by day. [0003] Most radiopharmaceuticals used in positron emission tomography employ labeling of molecules such as water, oxygen, carbon dioxide, glucose, amino acids that participate in the specific metabolism of the organism[ 18 F] fluorine (fluoride), [ 11 C] carbon (carbon), [ 15 O] oxygen (oxygen) or [ 13 N] nitrogen (nitrogen) and other chemical techniques. For example, [C 11 ] Methi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K51/10C07K16/28
CPCC07K16/2848C07K2317/569A61K51/1045C07K2317/22G01N2800/7014Y02A50/30C07K16/2839C07K2317/56C07K2317/70A61K51/1027
Inventor 张基堉金灿宇洪官秀李炫昇金县珉
Owner KOREA BASIC SCI INST
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