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68 Ga-labeled eaca-modified c-met molecular imaging probe and its preparation and application

A 68ga-nota-eaca-ah111972, 68ga technology, applied in the field of biomedicine, can solve the problems of high background signal of immunogenicity, weak penetration ability of probe signal, only suitable for superficial organs, etc. Retention ability, improve membrane penetration ability, and reduce the effect of radiation damage

Active Publication Date: 2020-07-03
HARBIN MEDICAL UNIVERSITY
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  • Claims
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Problems solved by technology

Its shortcomings are obvious. First, monoclonal antibodies are slowly cleared in vivo due to their large molecular weight (>150KDa), and their half-life can be as long as several weeks, and their immunogenicity tends to cause high background signals; secondly, fluorescence Labeled probes have weak signal penetration ability and are only suitable for superficial organs, so it is difficult for clinical transformation

Method used

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  • <sup>68</sup> Ga-labeled eaca-modified c-met molecular imaging probe and its preparation and application
  • <sup>68</sup> Ga-labeled eaca-modified c-met molecular imaging probe and its preparation and application
  • <sup>68</sup> Ga-labeled eaca-modified c-met molecular imaging probe and its preparation and application

Examples

Experimental program
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Effect test

Embodiment 168

[0048] Example 1 68 Ga-NOTA-EACA-AH111972 and its preparation

[0049] 1) Mix lysine and targeting polypeptide AH111972 at a molar ratio of 2.5:1.5, dissolve in 1 mM DMF (dimethylformamide), and mix in 2.5 equivalents of N, N-diisopropylethylamine (DIPEA) and 1.5 Under the action of equivalent diethyl clodronate (DECP), the product of the first step is obtained by amino condensation reaction, that is, the product (II) modified by lysine to AH111972, such as figure 1 Formula II;

[0050] 2) The product of the first step obtained in step 1) is reacted with aminocaproic acid to obtain the product of the second step through amino condensation reaction and subjected to Fmoc protection to obtain compound (Ⅲ), such as figure 1 Formula III, increasing its fat solubility;

[0051] 3) Remove the protecting group Fmoc from the compound (III) obtained in step 2) under the condition of 20% piperidine in DMF solution to obtain the product of the third step;

[0052] 4) Preparation of NO...

Embodiment 2

[0057] Example 2 Probe 68 In vivo targeting validation of Ga-NOTA-EACA-AH111972

[0058] NSCLC cell line Hcc827 with high expression of c-Met and NSCLC cell line H1299 with no expression of c-Met were used to establish tumor models in nude mice (BALB / c female mice, 5 weeks old, about 20 g, 2× 10 6 The number of cells is implanted subcutaneously on the right shoulder, and the tumor volume is about 300mm after about 4 weeks 3 for in vivo imaging experiments), injected into the mouse tail 68 After Ga-NOTA-EACA-AH111972 probe solution (5MBq~7.2MBq), PET / CT scanning (Discovery 790Elite, GE healthcare) was performed for 1h and 2h under isoflurane-oxygen anesthesia, and the scanning time was 5min. Processing platform AW4.6 software (GE Healthcare).

[0059] Imaging results such as figure 2 As shown, Hcc827 tumor uptake probe was significantly higher than the background, and significantly higher than H1299, indicating that the probe 68 Ga-NOTA-EACA-AH111972 can specifically ide...

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Abstract

The invention belongs to the field of biological medicine, specially relates to a cyclic polypeptide with c-Met targeting, in particular to a radionuclide 68Ga labeled c-Met tracer agent 68Ga-NOTA-EACA-AH111972 and a preparation method thereof, and further relates to application of the tracer agent as a non-small-cell lung cancer (NSCLC)PET imaging photographic developer. The probe has the advantages that labeling of the radionuclide 68Ga in the short half-life period is adopted, not only can the unnecessary radiation damage be reduced, but also in-vitro imaging equipment PET of the probe canprovide high-resolution images, and on the basis, corresponding structural optimization is carried out to increase the lipid solubility, thereby improving the transmembrane ability and in-vivo retention ability.

Description

Technical field: [0001] The present invention relates to biologically active cyclic polypeptides, in particular to radionuclides with c-Met targeting 68 Ga-labeled tracer 68 Ga-NOTA-EACA-AH111972 and a preparation method thereof, the invention also relates to the application of the tracer as a non-small cell lung cancer (NSCLC) PET imaging agent, which belongs to the field of biomedicine. Background technique: [0002] Hepatocyte growth factor receptor (c-Met) plays an important role in the occurrence and development of tumors. The targeted inhibitors of c-Met have been extensively carried out in clinical trials, and some drugs have completed clinical transformation and achieved important results. Studies have shown that the abnormal expression level and expression state of c-Met are closely related to the response to molecular targeted therapy, therapeutic effect and prognosis, so it is particularly important to accurately evaluate the abnormal expression level and express...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/00C07K1/06A61K51/08A61K103/34A61K101/02A61K103/00
CPCY02P20/55
Inventor 申宝忠孙夕林王凯韩兆国刘杨杨丽丽
Owner HARBIN MEDICAL UNIVERSITY
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