Fluorescence and lutetium-177 double-labeled biomolecule as well as preparation method and application thereof

A biomolecular, dual-labeling technology, used in chemical instruments and methods, fluorescence/phosphorescence, material analysis by optical means, etc., can solve the problems of limited data and rare research on such biomolecules, and achieve long residence time, easy to use. Separation and purification, mild reaction conditions

Pending Publication Date: 2020-12-22
INST OF NUCLEAR PHYSICS & CHEM CHINA ACADEMY OF
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

It will have positive significance for the scientific research and practical application of radiotargeted drugs and related biologic

Method used

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  • Fluorescence and lutetium-177 double-labeled biomolecule as well as preparation method and application thereof
  • Fluorescence and lutetium-177 double-labeled biomolecule as well as preparation method and application thereof
  • Fluorescence and lutetium-177 double-labeled biomolecule as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] In this example, a method for preparing a hyaluronic acid polymer compound double-labeled with lutetium-177 and Alexa Fluor 647 is provided, and the steps are as follows:

[0034] (1) Dissolve 100 mg of hyaluronic acid in 12 mL of pure water, add 8.8 mg of functionalized linker small molecule 3,3'-dithiobis(propionic hydrazide) (3,3'-Dithiobis(propionic hydrazide)) and Stir and mix, then add the HoBt solution formed by dissolving 35.5mg 1-hydroxybenzotriazole (HoBt) in 0.5mL DMSO and stir and mix; adjust the pH value of the resulting mixed solution to 4.7 with 1mol / L hydrochloric acid, Then 35mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) was added, and the reaction was stirred at room temperature for 8h;

[0035] (2) Adjust the pH value of the reaction solution obtained in step (1) to 8.7 with 1mol / L sodium hydroxide, then add 25mg dithiothreitol (DTT), and adjust with 1mol / L hydrochloric acid after stirring at room temperature for 6h When the...

Embodiment 2

[0039] In this example, the in vitro stability of the lutetium 177 / fluorescence double-labeled hyaluronic acid compound prepared in Example 1 was investigated.

[0040] Take lutetium 177 / Alexa Fluro 647 fluorescent double-labeled hyaluronic acid macromolecular compound 0.1mL (1mg / ml) of Example 1, place them in 1mL of PBS, DMEM culture solution and serum respectively, and place them at a constant temperature of 37°C for 2h. After 8h and 24h, the solution was taken respectively to detect the label stability by iTLC. The results showed that the hyaluronic acid polymer compound with lutetium 177 / Alexa Fluro647 fluorescent double labeling had good stability within 24 hours.

Embodiment 3

[0042] In this example, the in vivo imaging of lutetium 177 / fluorescent double-labeled hyaluronic acid compound was investigated.

[0043] Inject 0.1 mL of lutetium 177 / AlexaFluro 647 fluorescent double-labeled hyaluronic acid polymer compound with a concentration of 2.5 mg / ml into small cell lung cancer tumor mice through the tail vein, and observe the fluorescent signal at 180 hours. The result shows that the fluorescent label It has good stability in vivo, and it can be observed that the targeting molecule reaches the target tumor location and stays in the tumor for a long time.

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Abstract

The invention provides a fluorescence and lutetium-177 double-labeled biomolecule as well as a preparation method and application thereof, which belong to the technical field of biofunctional molecular markers. According to the double-labeled biomolecule, fluorescence and a diphosphate functional group are adopted to modify the biomolecule at the same time to obtain a compound I, and meanwhile, the compound I is further radiolabeled by utilizing the interaction between diphosphate and lutetium-177 to obtain a compound II, namely the double-labeled biomolecule; and the biomolecule is any bioactive macromolecule with a carboxyl group. The biomolecule has good in-vivo stability, can be used for low-cost fluorescence imaging or single-photon emission computed tomography imaging tracing with better tissue penetrability, and can also be used for radioactive therapy of various indications according to the characteristics of labeled biomolecules. The structural formula of the fluorescence andlutetium-177 double-labeled biomolecule is shown in the specification.

Description

technical field [0001] The invention belongs to the technical field of biofunctional molecular labeling, and specifically relates to a fluorescent and lutetium-177 double-labeled biomolecule as well as a preparation method and application thereof. Background technique [0002] At present, the commonly used metal radionuclide chelating ligands are mainly polycyclic structure molecules, which are relatively expensive, and usually require a high reaction temperature (>50°C) for metal radioactive chelation labeling. Bisphosphonates can be synthesized independently, with simple steps, no complicated purification process, and high yield. Previous reports have shown that bisphosphonates can bind multivalent cations such as Ca 2+ , Mg 2+ etc., and this kind of bisphosphonate molecules can be modified by terminal functionalization, and combined with biomolecules with sulfhydryl groups by click chemical reaction to obtain bisphosphonate-modified biofunctional molecules. [0003]...

Claims

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Application Information

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IPC IPC(8): C09K11/06G01N21/64A61P35/00
CPCC09K11/06G01N21/6428A61P35/00C09K2211/1466
Inventor 杨夏杨宇川彭述明王静卓连刚廖伟赵鹏王关全阚文涛
Owner INST OF NUCLEAR PHYSICS & CHEM CHINA ACADEMY OF
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