A spect imaging agent and its marking precursor and its preparation method, composition and use

The technology of an imaging agent and a composition is applied in the field of SPECT imaging agent and its labeling precursor and its preparation, and can solve the problem that the imaging agent cannot distinguish the expression level of PD-L1, does not use a pre-localization method, and is rich in blood supply. Organ imaging is obvious and other problems, to achieve the effect of easy clinical transformation, high purity of marker radiochemistry, and low cost

Active Publication Date: 2022-07-19
ZHONGSHAN HOSPITAL FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The radioimmunoimaging and treatment of radionuclide-labeled direct macromolecules (such as antibodies) has the following problems: large molecular weight, long circulation time in the body; long retention time, large side effects; obvious development of rich blood supply organs; low target / background
The disadvantage is that the radioactive uptake in the blood is still high 48h after injection of the imaging agent, which is the basis of our study using click chemistry
[0008] So far, based on domestic and foreign studies on radionuclide-labeled antibodies targeting PD-1 / PD-L1, it can be found that: no pre-localization method has been used; imaging agents cannot distinguish between different cell lines of the same tumor. PD-L1 expression level

Method used

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  • A spect imaging agent and its marking precursor and its preparation method, composition and use
  • A spect imaging agent and its marking precursor and its preparation method, composition and use
  • A spect imaging agent and its marking precursor and its preparation method, composition and use

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Experimental program
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Effect test

Embodiment 1

[0044] Synthesis of compound 3:

[0045]

[0046] To a solution of compounds 1 (250 mg, 1.11 mmol, HCl) and 2 (191 mg, 1.67 mmol) in 2.5 mL of dichloromethane was added triethylamine (339 mg, 3.35 mmol). The reaction solution was stirred at 20°C for 1 hour. The reaction was detected by TLC, and the reaction of the raw materials was complete. The reaction was concentrated under reduced pressure, and the mixture was stirred with silica gel for column purification (100-200 mesh silica gel, DCM:MeOH=50:1) to obtain compound 3 (250 mg, yield 70.5%) as a red solid.

Embodiment 2

[0048] Synthesis of compound 4:

[0049]

[0050] HATU (176 mg, 465 umol) and DIEA (150 mg, 1.16 mmol) were added to a solution of compound 3 (140 mg, 464 umol) in 5 mL of dichloromethane. After stirring at 20 °C for 15 min, NH was added. 2 -PEG11-NHBoc (250 mg, 387 umol), stirred for another hour at 20°C. TLC detection showed that the reaction of the raw materials was complete. Concentrate under reduced pressure, and purify on a large plate (SiO2, DCM:MeOH=10:1) to obtain compound 4 (320 mg, yield 81.7%) as a red oil.

Embodiment 3

[0052] Synthesis of compound 5:

[0053]

[0054] To a solution of compound 4 (320 mg, 344 umol) in hexyl acetate (3 mL) was added a 4M ethyl acetate solution (86.2 uL), and stirred at 20° C. for 30 min. TLC detection showed that the reaction of the raw materials was complete. Spin to dryness under reduced pressure to obtain compound 5 (260 mg, yield 81.9%) as a red oil, which was directly used in the next reaction.

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Abstract

The invention relates to a SPECT imaging agent and a labeling precursor thereof, and discloses a preparation method and application of the above-mentioned SPECT imaging agent and its labeling precursor; the invention also discloses a composition containing the above-mentioned SPECT imaging agent. The composition also includes an antibody chelate targeting PD-L1. The SPECT imaging agent and its labeling precursor of the present invention have a brand-new chemical structure, have a very high reaction rate constant with the antibody chelate targeting PD-L1, can be used for labeling different radionuclides, are easy to clinical transformation, and can be used in clinical applications. No immune response in the body and low chemical toxicity.

Description

technical field [0001] The invention relates to the technical field of radiopharmaceutical chemistry, in particular to a SPECT imaging agent and a labeling precursor thereof, as well as a preparation method, composition and use thereof. Background technique [0002] The programmed cell death protein-1 / programmed cell death ligand-1 (programmed cell deathprotein-1 / programmed cell death ligand-1, PD-1 / PD-L1) signaling pathway is a negative immune co-stimulation discovered in recent years Molecules have become new targets for tumor immunotherapy due to their involvement in tumor immune escape. PD-1 is an inducible protein that does not express PD-1 in naive T cells and is up-regulated after T cell activation. The expression of PD-1 is mainly concentrated in immune cells. PD-L1 is an antigenic determinant named CD274 or B7-H1, encoded by the CD274 gene on chromosome 9, PD-L1 is a transmembrane protein with a molecular weight of 40 kDa. PD-L1 is expressed in APC, activated CD4...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K51/06A61K51/04C08G65/333A61K103/10
CPCA61K51/06A61K51/0495C08G65/33396
Inventor 邱琳程登峰石洪成林卿玉付哲荃谭辉王婷婷
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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