Targeted tumor PD-L1 PET imaging agent as well as labeled precursor, preparation method and application thereof

A PET imaging agent, PD-L1 technology, applied in the preparation method of peptides, anti-tumor drugs, preparations for in vivo tests, etc., can solve the problems of radionuclide therapeutic drug reporting, etc., achieve good binding specificity, design Scientific, good stability effect

Pending Publication Date: 2021-11-02
THE AFFILIATED HOSPITAL OF SOUTHWEST MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

A variety of common clinical tumors, including non-small cell lung cancer, breast cancer, and melanoma, have increased expression levels of PD-L1. The development of radionuc...

Method used

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  • Targeted tumor PD-L1 PET imaging agent as well as labeled precursor, preparation method and application thereof
  • Targeted tumor PD-L1 PET imaging agent as well as labeled precursor, preparation method and application thereof
  • Targeted tumor PD-L1 PET imaging agent as well as labeled precursor, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Synthesis of DOTA-SETSKSF

[0038] The preparation method is a conventional polypeptide Fmoc synthesis method, linking DOTA through amide bonds. DOTA-SETSKSF mass spectrometry detection chart is attached figure 1 shown.

Embodiment 2

[0040] This embodiment discloses the compound of formula II 68 Synthesis of Ga-DOTA-SETSKSF, specifically:

[0041] Put 25 μg of compound DOTA-SETSKSF of formula I dissolved in 100 μL of distilled water into the reaction bottle, add 750 μL of 0.25M sodium acetate and 3 mL of freshly washed 68 Ga eluent ( 68 Ga was rinsed in 0.05M hydrochloric acid solution), the pH value of the reaction solution was about 4.0, and after mixing, it was reacted at 80°C for 10 minutes. After the reaction was completed, the C18 column was used for purification. The radiochemical purity of the product was greater than 99% as detected by radio-HPLC. The radioactive labeling reaction equation is as follows:

[0042]

[0043] Radio-HPLC test results are attached figure 2 Shown, among them, the picture above is the result of the radioactivity detector, and the place where the peak time Rt=13.6min is 68 The emission peak of Ga-DOTA-SETSKSF; the figure below is the result of the ultraviolet detec...

Embodiment 3

[0045] This embodiment discloses the compound of formula II of the present invention 68 In vitro stability test of Ga-DOTA-SETSKSF, specifically:

[0046] With embodiment 2 gained 68 About 100 μCi of Ga-DOTA-SETSKSF were respectively placed in 100 μL of 0.9% normal saline and 0.1% BSA, mixed well and stored at 37°C. Samples were taken at 30min, 1h, 2h and 4h, and the changes in radiochemical purity were checked by analytical Radio-HPLC. the result shows 68 The radiochemical purity of Ga-DOTA-SETSKSF is more than 98% after 4h, good stability and almost no decomposition.

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Abstract

The invention discloses a tumor PD-L1 targeting PET imaging agent as well as a labeled precursor, a preparation method and application thereof, and belongs to the technical field of radiopharmaceutical chemistry. The structure of a labeled precursor of the tumor PD-L1 targeting PET developer is shown as a formula I, and the structure of the tumor PD-L1 targeting PET developer is shown as a formula II. According to the invention, a bifunctional chelating agent DOTA and a cyclic peptide inhibitor SETSKSF are creatively connected together, and a labeled precursor of a PET imaging agent of a targeted tumor PD-L1 as shown in a formula I is synthesized. After the precursor compound is marked with Ga-68, a compound shown in a formula II can be obtained, and the compound has good stability, excellent pharmacokinetics, good binding specificity with tumor PD-L1 and easy synthesis.

Description

technical field [0001] The invention relates to the technical field of radiopharmaceutical chemistry, in particular to a PET imaging agent targeting tumor PD-L1, its labeled precursor, its preparation method and application. Background technique [0002] In recent years, tumor immunotherapy has developed rapidly and has shown good application prospects in tumor treatment. Programmed cell death protein-1 (Programmed cell death protein 1, PD-1) and its ligand, the programmed cell death ligand-1 (Programmed cell death ligand-1, PD-L1) signaling pathway is the cancer cell for The main immune checkpoint pathway for generating and maintaining immune tolerance, the PD-1 / PD-L1 signaling pathway has become a new target for tumor immunotherapy. As a member of the B7 family, PD-L1 is expressed in normal nonlymphoid organs and is upregulated in activated T cells, antigen-presenting cells, and non-hematopoietic cells. Abnormal expression of PD-L1 in tumor cells can impair the body's an...

Claims

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Application Information

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IPC IPC(8): C07K7/06C07K1/13A61K51/04A61K51/08A61P35/00A61K103/00
CPCC07K7/06A61K51/0482A61K51/08A61P35/00Y02P20/55
Inventor 邱琳兰莲君刘汉香邓嘉赵岩冯悦吕太勇邢乃果孙占良王力周志军陈跃
Owner THE AFFILIATED HOSPITAL OF SOUTHWEST MEDICAL UNIV
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