A kind of tumor vegfr-3 molecular imaging agent and its application

A technology of VEGFR-3 and imaging agent, which is applied in the field of nuclear medicine imaging, and can solve the problems of affecting the imaging effect, loss of polypeptide LARGR activity and function, and inconspicuous development of target organs, etc.

Active Publication Date: 2018-07-20
武汉凯德维斯医学检验实验室有限公司
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  • Abstract
  • Description
  • Claims
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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 five amino acid peptides are 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 active 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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  • A kind of tumor vegfr-3 molecular imaging agent and its application
  • A kind of tumor vegfr-3 molecular imaging agent and its application
  • A kind of tumor vegfr-3 molecular imaging agent and its application

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Experimental program
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Effect test

Embodiment 1

[0057] Embodiment 1 preparation 68 Ga-DOTA-TMVP1′

[0058] 1. Synthetic polypeptide DOTA-TMVP1'

[0059] Polypeptide DOTA-TMVP1′ was synthesized using peptide solid-phase synthesis technology, that is, a polypeptide with a structural formula of DOTA-GGG-Cyclic (CGLARGRGC). ) The purity of the polypeptide is 95%. Its molecular weight is 1514.65 and its mass is 10 mg, detected by RP-HPLC and MS techniques.

[0060] 2. Synthesis 68 Ga-DOTA-TMVP1′

[0061] (1) 68 Ga leaching

[0062] Use a plastic 5mL syringe to draw 5mL of 0.1M concentrated hydrochloric acid (it is forbidden to use metal products such as iron needles to contact concentrated hydrochloric acid, because the reaction between metal products and hydrochloric acid makes the solution contain metal ions, which affects 68 Ga label).

[0063] Insert a syringe filled with 5 mL of 0.1M concentrated hydrochloric acid into the 68 Ge / 68 A Ga generator (ITG, Germany) rinses the inlet, followed by a slow bolus injection....

Embodiment 2

[0078] Embodiment 2 in vitro stability test:

[0079] Get the prepared 37MBq embodiment 1 68 Ga-DOTA-TMVP1' was placed in cysteine, normal 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 The radiochemical purity (RCP) of different samples with different incubation times was determined by HPLC and iTLC-SG.

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

Embodiment 3

[0081] The establishment of embodiment 3 tumor model and PET imaging

[0082] 1. To establish a subcutaneous tumor model of cervical cancer:

[0083] (1) Cell culture

[0084] Cervical cancer cell lines C-33A, HeLa and SiHa (purchased from ATCC Cell Bank, USA) were cultured with DMEM medium (Gibco, ThermoFish Company, USA) containing 10% serum by volume fraction (37°C, 5% CO 2 incubator), when the cell confluency reaches 80%, it is digested with trypsin solution (containing 0.25% trypsin and 0.1% EDTA by mass fraction), and centrifuged at 800rpm for 5 minutes after terminating the digestion with DMEM medium , remove the supernatant, resuspend with PBS (pH 7.4), centrifuge again at 800rpm for 5 minutes, resuspend with PBS (pH 7.4), count the cells, and the result is 1×10 7 / mL. (Because PBS is a conventional phosphate buffered saline in the art, the recipe is not listed in detail.)

[0085] (2) Subcutaneous tumor model

[0086] BALB / c-nude mice aged 3-4 weeks were purchase...

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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 tumor VEGFR-3 molecular imaging agent and application thereof. Background technique [0002] Cervical cancer, ovarian cancer and endometrial cancer are the three most common malignant tumors in gynecology. Among them, ovarian cancer has the characteristics of not being diagnosed early, easy to relapse and poor prognosis. Cervical cancer is the most common gynecological malignancy. 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 ranks fourth among all cancers and ranks second among female cancers. Therefore, there is an urgent need to develop new tumor imaging agents and new effective targeted drugs to achieve early diagnosis and personalized treatment! [0003] Tumor occurrence and...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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