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Multi-modal leucocyte molecule probe compound and its preparation method and use

A molecular probe and compound technology, applied in the field of multifunctional probe compounds, can solve the problems of low sensitivity, poor specificity of inflammation, high cost, etc.

Active Publication Date: 2016-04-27
厦门东风精准医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantage of FDG / PET is that it has poor specificity for inflammation and is only used in some specific pathological states
Since the 1970s, 111 In / 99m Tc-WBC is still the gold standard reference for inflammation imaging[5]. The labeled white blood cells can spontaneously seek and gather at the site of inflammation, but the operation is complicated, the cost is high, and the sensitivity is low. 111 In / 99m The report of Tc-WBC used in aseptic inflammation imaging

Method used

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  • Multi-modal leucocyte molecule probe compound and its preparation method and use
  • Multi-modal leucocyte molecule probe compound and its preparation method and use
  • Multi-modal leucocyte molecule probe compound and its preparation method and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] Embodiment 1: Use solid-phase chemical method to synthesize double label probe precursor compound cFLFLF-Fl-HYNIC (formula III) and cFLFLF-Fl-NOTA (formula V), as scheme 1:

[0070] Using a peptide synthesizer, through standard Fmoc chemistry, compound 1 is gradually coupled on wangresin, and after removing the protective group MTT of the side chain, it is coupled with Fmoc-N-amido-PEG24-Acid to generate compound 2, and further removed Remove Fmoc protection and couple with Fmoc-Cys(Trt)-OH to generate compound 3. After removing Fmoc protection on the structure of compound 3, couple with NHS-HYNIC-Boc or p-SCN-Bn-NOTA respectively, and then in the mass In 1% trifluoroacetic acid-dichloromethane, wangresin was cleaved and the protecting group Trt on the cysteine ​​side chain thiol was removed to generate compound 4 (cFLFLFK-PEG24(SH)-HYNIC) and compound 5, respectively. (cFLFLFK-PEG24(SH)-NOTA). After HPLC purification, the sulfhydryl groups on compound 4 and compound 5...

Embodiment 2

[0072] Example 2, the ECT probe precursor compound cFLFLF-PEG24-HYNIC (formula VIII) was synthesized using solid phase chemistry, and the PET probe precursor compound cFLFLF-PEG24-NOTA (formula X) was shown in Scheme 2:

[0073] Using a peptide synthesizer, through standard Fmoc chemistry, compound 2 was gradually coupled on wangresin, and after further removal of Fmoc protection, compound 6 and Compound 7, then cut wangresin in 1% trifluoroacetic acid-dichloromethane to generate ECT probe precursor compound cFLFLF-PEG24-HYNIC (formula VIII) and PET probe precursor compound cFLFLF-PEG24 -NOTA (Formula X) (as shown in Scheme 2), purified by HPLC, and freeze-dried to obtain the target compound. The molecular weight of this compound was identified by using a MULDI-TOF mass spectrometer. The calculated and experimental molecular weights of cFLFLF-PEG24-HYNIC (Formula VIII) were 2,405 and 2,404, respectively; the calculated and experimental molecular weights of cFLFLF-PEG24-NOTA (...

Embodiment 3

[0076] Embodiment 3, synthetic multimodal leukocyte molecular probe compound cFLFLF-Fl- 99m Tc (formula IV), such as scheme 3:

[0077] Take 50 μg of cFLFLF-Fl-HYNIC (formula III), weigh 6.7 mg of tricine into an eppendorf vial, add 200 μL of normal saline to dissolve, then add 200 μL of TPPTS (5 mg / mL aqueous solution), and finally add 20 μL of 1 mg / mL stannous chloride hydrochloric acid solution (1M hydrochloric acid solution), then immediately add 0.4mL[ 99m Tc] pertechnetate (20mCi), react at 60°C for 10 minutes, let stand at room temperature for 10 minutes, use a C18 separation column (Sep-Paklightcartridge) to separate the salt in the reaction mixture, and finally use 1mL ethanol to elute the labeled compound, then add 1mL normal saline was mixed to obtain the cFLFLF-Fl- to be injected 99m Tc (Formula IV).

[0078] Scheme 3 chemical synthesis route:

[0079]

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Abstract

The invention relates to a preparation method and use of a multi-modal leucocyte molecule probe compound (shown in the formula I). The multi-modal leucocyte molecule probe compound has a plurality of imaging functions, is convenient for mutual verification of clinical research and a treatment method, is conducive to clinical application conversion acceleration, has a good market development prospect and provides possibility for instant assessment for tracking leucocyte activation time, transfer and positioning. The multi-modal leucocyte molecule probe compound creatively provides a high-specificity, simple and easy multifunctional imaging method for research and clinical detection of various immunization leucocytes.

Description

technical field [0001] The invention relates to a series of multifunctional probe compounds targeting formyl peptide receptors and capable of in vivo leukocyte contrast tracing and in vitro pathological tissue color development. This type of molecular probe compound is composed of three parts: formyl peptide receptor targeting small molecule peptide, nuclear imaging isotope and small molecule fluorescent light-emitting group. It integrates the functions of living nucleus, light imaging, tissue and blood color analysis. It can be applied to nuclear imaging, fluorescence imaging, color development of pathological tissues, and blood analysis of various aseptic and bacterial inflammations in clinical practice. The present invention relates to the series of compounds and synthesis methods, and the pharmacological effects thereof have been further verified through animal bacteria and aseptic inflammation model experiments. Background technique [0002] At present, it is still dif...

Claims

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Application Information

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IPC IPC(8): C09K11/06C07K7/06A61K49/00A61K47/42A61P29/00G01N21/64
CPCY02P20/55
Inventor 邵立潘东风吴华
Owner 厦门东风精准医药科技有限公司