Radioactive technetium-labeled PD-L1 targeting peptide, and preparation method and applications thereof

A PD-L1, targeting peptide technology, applied in the biological field, can solve the problems of missed diagnosis and misinterpretation, and achieve the effects of slow blood clearance, slow tissue penetration, and large molecular weight

Pending Publication Date: 2020-06-23
THE SECOND AFFILIATED HOSPITAL OF ANHUI MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

③The IHC method may lead to misinterpretation or even missed diagnosis due to heterogeneous expression within or between tumor lesions and the preparation of pathological sections.

Method used

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  • Radioactive technetium-labeled PD-L1 targeting peptide, and preparation method and applications thereof
  • Radioactive technetium-labeled PD-L1 targeting peptide, and preparation method and applications thereof
  • Radioactive technetium-labeled PD-L1 targeting peptide, and preparation method and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1. Preparation of radioactive technetium-labeled PD-L1 targeting polypeptide and detection of labeling rate

[0039] 1. Preparation and identification of SKI small molecule peptides

[0040] DTPA is connected to the amino terminal of the PD-L1 targeting polypeptide shown in SEQ ID No.1 to obtain the SKI small molecule polypeptide ( figure 1 ).

[0041] Mass spectrometry and HPLC detection of SKI small molecule peptides.

[0042]The specific conditions of mass spectrometry are: operation mode: linear; extraction mode: delay; polarity: anode acquisition control: manual; acceleration voltage: 20000 volts; grid voltage: 95%; extraction delay time: 200 nanoseconds; laser number: 50 / Spectrum; laser intensity: 2865; laser frequency: 3.0 Hz; calibration type: missing.

[0043] The specific conditions of high performance liquid chromatography (HPLC) are:

[0044] High performance liquid chromatography column (HPLC Column): Agela (250×4.6mm I.D.) C18, detection wavel...

Embodiment 2

[0055] Stability detection of the radioactive technetium-labeled PD-L1 targeting polypeptide prepared in Example 2 and Example 1

[0056] The radioactive technetium-labeled PD-L1 targeting polypeptide prepared in Example 1 ( 99m The stock solution of Tc-SKI) was placed at room temperature and subjected to radiochemistry for 30min, 1h, 2h, and 4h respectively, and the radiochemical purity was determined to evaluate the stability. Take paper chromatography and measure with nuclide chromatography 99m For the radiochemical purity of Tc-SKI, the specific operation is the same as before (labeling rate detection method).

[0057] The result is as Figure 4 As shown, it can be seen from the figure that 99m The radiochemical purity of Tc-SKI within 4 hours was greater than 90% (n=3), which indicated that the radioactive technetium-labeled PD-L1 targeting polypeptide prepared in Example 1 had better stability.

Embodiment 3、99

[0058] Embodiment 3, 99m Biodistribution of Tc-SKI triple-negative breast cancer mouse model

[0059] 1. Cell culture and animal model construction

[0060] It has been reported in the literature that the MDA-MB-231 cell line is a triple-negative breast cancer with high expression of human PD-L1. The cells are routinely cultured. Under the premise of aseptic operation principle, the concentration was 1×10 7 / 100μL of cell suspension was inoculated into the armpit of mice by subcutaneous injection to construct a subcutaneous tumor animal model. When the tumor diameter was 0.8-1cm, the 99m Tc-SKI SPECT imaging study.

[0061] two, 99m Tc-SKI SPECT planar imaging

[0062] Anesthetized with isoflurane gas, after successful anesthesia, nude mice were fixed on the board in prone position, and SPECT imaging was performed.

[0063] Experimental group: prepared in Example 1 by injecting 7.4MBq (200μCi, 100μl) into the tail vein 99m Tc-SKI.

[0064] Monoclonal antibody blocking...

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Abstract

The invention discloses radioactive technetium-labeled PD-L1 targeting peptide, and a preparation method and applications thereof. The provided preparation method of the PD-L1 targeting peptide includes the following steps: connecting the amino terminal of the PD-L1 targeting peptide with DTPA, and then using radioactive technetium to perform labeling. The labeling rate of the provided preparationmethod can reach 94.00% + / - 1.47%, which is greater than 90%, so that the preparation method is good in stability, and has PD-L1 targeting specificity and biosafety. Layered screening can be performed on patients with different PD-L1 expression levels; objective bases can be provided for screening potential PD-L1 mAb treatment beneficiary groups and avoiding fatal immune-related adverse reactionscaused by PD-L1 mAb; and efficacy response can be monitored, so that the PD-L1 targeting peptide and the preparation method have important significance on enhancing the effectiveness and safety of drugs.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a radioactive technetium-labeled PD-L1 targeting polypeptide and its preparation method and application. Background technique [0002] Immunotherapy based on PD-L1 / PD-1 pathway blockade has shown promising prospects in clinical practice. It is to block immune escape and activate the immune system to kill tumor cells. However, clinical studies have shown that different individuals have different sensitivity and tolerance to the same immune-targeted therapy, and only about 20% of tumor patients can benefit from a single anti-PD-1 / PD-L1 immunotherapy; and immune Treatment-induced immune-related adverse reactions (such as immune myocarditis) should not be ignored. Therefore, exploring the basic mechanism of PD-L1 inhibitor therapy and pre-screening the best benefit patient population through the expression level of the biological target PD-L1 may be expected to optimize the treatment pl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/00C07K1/13A61K51/08A61K103/10
CPCC07K14/001A61K51/08
Inventor 庞小溪李飞常文瑞袁清玥李腾宇
Owner THE SECOND AFFILIATED HOSPITAL OF ANHUI MEDICAL UNIV
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