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Novel tumor VEGFR-3 molecular photographic developer and application thereof

A technology of VEGFR-3 and imaging agent, applied in the field of nuclear medicine imaging, can solve the problems of unknown, affecting the imaging effect, not involved, etc.

Active Publication Date: 2015-12-09
武汉凯德维斯医学检验实验室有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Previous experiments have shown that this five-amino acid peptide has a high affinity for lymphatic vessels and has the potential to be used as a molecular targeted diagnostic agent, but it has not been involved in how to apply it to tumor diagnosis. The effect of the application of the peptide LARGR in PET imaging is also unknown
[0010] In addition, if the peptide segment of five amino acids is directly applied to the imaging technology, there are many problems, because the chelating agent and radionuclide affect the spatial structure of the core sequence, resulting in the loss of the activity function of the polypeptide LARGR; the radiopharmaceutical in vivo Metabolic radiation will affect its imaging effect. For example, the combination of radiopharmaceuticals and serum proteins in the blood leads to a high background in whole-body imaging and the development of target organs is not obvious; there are a large number of proteases and polypeptide enzymes in the body, which leads to the stability of polypeptides in vivo. influences

Method used

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  • Novel tumor VEGFR-3 molecular photographic developer and application thereof
  • Novel tumor VEGFR-3 molecular photographic developer and application thereof
  • Novel tumor VEGFR-3 molecular photographic developer and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Example 1 Preparation 68 Ga-DOTA-TMVP1′

[0058] 1. Synthetic peptide DOTA-TMVP1′

[0059] The peptide DOTA-TMVP1′ is synthesized by the peptide solid-phase synthesis technology, that is, the peptide with the structural formula DOTA-GGG-Cyclic (CGLARGRGC). The synthesis process is completed by Shanghai WuXi AppTec New Drug Development Co., Ltd. The synthesized DOTA-GGG-Cyclic (CGLARGRGC) ) The purity of the polypeptide is 95%, and its molecular weight is 1514.65 and the mass is 10 mg by RP-HPLC and MS techniques.

[0060] 2. Synthesis 68 Ga-DOTA-TMVP1′

[0061] (1) 68 Ga's rinse

[0062] Use a plastic product 5mL syringe to suck 5mL of 0.1M concentrated hydrochloric acid (it is contraindicated to use metal products such as iron needles to contact concentrated hydrochloric acid, because the reaction of metal products with hydrochloric acid causes the solution to contain metal ions, which affects 68 Ga mark).

[0063] Connect the syringe containing 5mL 0.1M concentrated hydrochlori...

Embodiment 2

[0078] Example 2 In vitro stability test:

[0079] Take 37MBq prepared in Example 1 68 Ga-DOTA-TMVP1' was placed in cysteine, saline and normal serum (referring to the serum of non-tumor patients), and incubated at 37°C for 30 minutes, 1 hour, 2 hours and 3 hours, and then used HPLC and iTLC-SG determine the radiochemical purity (RCP) of different samples at different incubation times.

[0080] Experimental results: figure 1 For detection by HPLC 68 Experimental results of the stability of Ga-DOTA-TMVP1' in physiological saline, HPLC detection 68 The residual time of Ga-DOTA-TMVP1' in physiological saline is 10.6min; figure 2 for 68 The verification result of the in vitro stability of Ga-DOTA-TMVP1′ was tested by HPLC and iTLC-SG 68 Ga-DOTA-TMVP1' has good stability in saline, cysteine ​​and normal serum, and it still reaches 92% after three half-lives.

Embodiment 3

[0081] Example 3 Establishment of tumor model and PET imaging

[0082] 1. Establish cervical cancer subcutaneous tumor model:

[0083] (1) Cell culture

[0084] Cervical cancer cell lines C-33A, HeLa and SiHa (purchased from ATCC Cell Bank, USA) were cultured in DMEM medium (Gibco, ThermoFish, USA) containing 10% serum at 37°C, 5% CO 2 Culture in incubator), when the cell confluence reaches 80%, digest with trypsin solution (containing 0.25% trypsin and 0.1% EDTA), stop the digestion with DMEM medium, and centrifuge at 800rpm for 5 minutes , Remove the supernatant, resuspend in phosphate buffered saline PBS (pH 7.4), centrifuge again at 800 rpm for 5 minutes, resuspend in PBS (pH 7.4), and count the cells, the result is 1×10 7 / mL. (Because PBS is a conventional phosphate buffer in the field, the formula is not listed in detail.)

[0085] (2) Subcutaneous tumor model

[0086] BALB / c-nude mice were taken 3-4 weeks old, and BALB / c-nude mice were purchased from Beijing Huafukang Biotechn...

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Abstract

The invention relates to a novel tumor VEGFR-3 molecular photographic developer, which comprises polypeptide with a structural formula 68Ga-DOTA-GGG-Cyclic (CGLARGRGC), wherein DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracarboxylic acid; the novel tumor VEGFR-3 molecular photographic developer is connected with the targeted VEGFR-3 molecular polypeptide under the chelation action of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracarboxylic acid, and is labeled with a radionuclide tracer 68Ga. The novel molecular diagnostic agent 68Ga-DOTA-TMVP1 minute for PET inspection fills the blank of a neogenesis lymphatic polypeptide photographic developer for inspecting tumors by PET, so that great assistance in clinical VEGFR-3 molecular diagnosis in the future and instruction of the individuation of a tumor patient is realized.

Description

Technical field [0001] The invention relates to the technical field of nuclear medicine imaging, in particular to a novel tumor VEGFR-3 molecular imaging agent and its application. Background technique [0002] Cervical cancer, ovarian cancer and endometrial cancer are the three most common malignant tumor diseases in gynecology. Among them, ovarian cancer has the characteristics of inability to diagnose early, easy to relapse and poor prognosis. Cervical cancer is the most common gynecological malignant tumor. With the popularization of early screening for cervical cancer, the prognosis of cervical cancer has improved significantly, but there are still relapsed and refractory cases. The mortality rate of cervical cancer in my country accounts for the fourth place in total cancer mortality and the second place in female cancer. Therefore, there is an urgent need to develop new tumor imaging agents and new effective targeted drugs to achieve the purpose of early diagnosis and pe...

Claims

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Application Information

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IPC IPC(8): A61K51/08A61K103/00
Inventor 马丁奚玲马湘一李飞张振中
Owner 武汉凯德维斯医学检验实验室有限公司
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