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Method for radiolabeling biological compound

A technology for biological compounds and radiolabeling, applied in the fields of radiopharmaceuticals and nuclear medicine, can solve the problems of research and clinical use of specific activity requirements, waste, low labeling yield, etc.

Pending Publication Date: 2020-10-23
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, although this two-step strategy has been widely used, its low labeling yield is its main disadvantage. The yield is 7-15%
This will cause a great waste of many expensive α-radiating body radionuclides, and at the same time have a great impact on the research and clinical use of radioimmunotherapy and other radiopharmaceuticals that require specific activity.

Method used

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  • Method for radiolabeling biological compound

Examples

Experimental program
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Effect test

Embodiment 1

[0034] Example 1 The HPLC analysis of the stability of DOTA-Mal and DOTA-SCN

[0035]Dissolve 1mg DOTA-Mal and DOTA-SCN in 50ul DMSO respectively, then dissolve in 1ml PBS, heat at 0 time and 60°C for 30min respectively, and use high performance liquid chromatography to analyze its components (liquid phase conditions: 40% acetonitrile / water, 1ml / min), the result is as figure 1 As shown, it can be seen that DOTA-Mal can remain stable, while DOTA-SCN is less stable during heating.

Embodiment 2Ac-225

[0036] Example 2Ac-225 labeled anti-PD-L1 monoclonal antibody

[0037] This embodiment uses DOTA-maleimide compound (Maleimido-mono-amide-DOTA, DOTA-Mal) as a bifunctional chelate, which can withstand high temperature reactions and remain stable, wherein DOTA can be combined with most common radioactive Nuclides are chelated.

[0038] The anti-PD-L1 monoclonal antibody (Adagene (Suzhou) Limited) was pretreated as follows: take 1.5 mg anti-PD-L1 monoclonal antibody, add 100 eq. TCEP to 0.1 mL PBS solution, and treat at 37 ° C for 1 h.

[0039] (1) Put 4eq. of DOTA-Mal in a 1.5ml centrifuge tube, add 10μCi[ 225 Ac]AcCl 3 Solution, and use 2M sodium acetate solution to adjust the pH to 5, and heat at 90°C for 5min.

[0040] (2) Then directly add the pretreated anti-PD-L1 monoclonal antibody to the product of step (1), and react at 37° C. for 1 h.

[0041] (3) After step (2), use PD-10 size exclusion resin (Sephadex G-25M) to purify according to its instructions, and the targe...

experiment example 1

[0042] Experimental Example 1 Radioactive Thin Layer Chromatography Radiation Imaging

[0043] In order to determine the yield of radioactive labeling in Example 2, this example provides a radioactive thin-layer chromatography radiographic imaging method.

[0044] Experimental method: Take 5ul samples of the corresponding experimental group and apply them on thin-layer chromatography paper, and use the corresponding developer to develop.

[0045] Developing agent I: 10mM EDTA / water, free radioactive metal ions and radioactive ion-chelates are at the front of the solvent, and the labeled antibody is at the origin.

[0046] Developing agent II: 100mM NaOH / 9% NaCl, the radioactive ion-chelate is at the front of the solvent, and the free radioactive metal ion and the labeled antibody are at the origin.

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Abstract

The invention relates to a method for radiolabeling a biological compound. The method comprises the following steps of performing chelation reaction on a bifunctional chelating agent modified with a maleimide group and radionuclide, and directly adding the biological compound to carry out coupling reaction, thereby obtaining the radiolabeled biological compound. The technical scheme adopts the maleimide group with excellent thermal stability, so that the bifunctional chelating agent can be chelated with radioactive metal ions under a high-temperature condition, the chelating reaction time is remarkably shortened, and the labeling efficiency is improved; and the product of the chelation reaction can be subjected to biological compound coupling without purification, and the method has the advantages of simple steps, convenience, high efficiency and high connection efficiency.

Description

technical field [0001] The invention relates to the technical fields of radiopharmaceuticals and nuclear medicine, in particular to a method for radionuclide labeling on biological compounds. Background technique [0002] Protein radiolabeling technology is one of the key technologies in current targeted radiotherapy and radioimmunotherapy. The current method usually uses a bifunctional chelating agent to connect functional groups with chelating functions such as DOTA, NOTA, and Dfo on the protein to achieve pre-modification of the protein, and then perform a radioactive metal nuclide labeling reaction. [0003] But for many therapeutic nuclides, such as β-radiator and α-radiator nuclides, they often have larger ionic radii, and chelation reactions are difficult to occur. For example, the classic α-radiator Bi-213 needs to react with DOTA at 60°C. Due to the sensitivity of proteins to temperature, the traditional method cannot achieve this labeling process. In order to sol...

Claims

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Application Information

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IPC IPC(8): C07K1/13
CPCC07K1/13
Inventor 刘志博陈俊艺
Owner PEKING UNIV
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