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Tumor targeting magnetic resonance contrast medium modified by chlorotoxin and preparation method and application thereof

A magnetic resonance contrast agent and tumor targeting technology, which is applied in the biological field to achieve the effects of high relaxation rate, reduced dosage and high value

Inactive Publication Date: 2012-07-11
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There have been many studies on the use of dendrimers as drug carriers in recent years, but there are few reports on the use of gadolinium-based MRI contrast agent carriers for the development of tumor diagnostic drugs

Method used

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  • Tumor targeting magnetic resonance contrast medium modified by chlorotoxin and preparation method and application thereof
  • Tumor targeting magnetic resonance contrast medium modified by chlorotoxin and preparation method and application thereof
  • Tumor targeting magnetic resonance contrast medium modified by chlorotoxin and preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0075] DGL (second generation) and PEG containing bifunctional groups were dissolved in phosphate buffer saline (PBS for short) at pH 8.0 according to the molecular ratio of 1:2, and stirred at room temperature for 2 h to generate DGL-PEG, which was removed by ultrafiltration. React with PEG and replace buffer with PBS pH 7.0. At the same time, CTX was reacted with Traut's reagent to introduce sulfhydryl groups, mixed with DGL-PEG at a molecular ratio of 1:1, stirred and reacted at room temperature for 24 hours, and unreacted CTX was removed by size exclusion chromatography to obtain DGL-PEG. PEG-CTX.

Embodiment 2

[0077] DGL (second generation) and PEG containing bifunctional groups were dissolved in PBS at pH 8.0 according to the molecular ratio of 1:5, and stirred at room temperature for 2 hours to generate DGL-PEG, and the unreacted PEG was removed by ultrafiltration and the buffer was replaced PBS pH 7.0. At the same time, CTX was reacted with Traut's reagent to introduce sulfhydryl groups, mixed with DGL-PEG at a molecular ratio of 1:1, stirred and reacted at room temperature for 24 hours, and unreacted CTX was removed by size exclusion chromatography to obtain DGL-PEG. PEG-CTX.

Embodiment 3

[0079] DGL (second generation) and PEG containing bifunctional groups were dissolved in PBS with pH 8.0 according to the molecular ratio of 1:10, and stirred at room temperature for 2 hours to generate DGL-PEG, and the unreacted PEG was removed by ultrafiltration and the buffer was replaced PBS pH 7.0. At the same time, CTX was reacted with Traut's reagent to introduce sulfhydryl groups, mixed with DGL-PEG at a molecular ratio of 1:1, stirred and reacted at room temperature for 24 hours, and unreacted CTX was removed by size exclusion chromatography to obtain DGL-PEG. PEG-CTX.

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Abstract

The invention belongs to the field of biotechnology, which relates to a tumor targeting magnetic resonance contrast medium modified by chlorotoxin and a preparation method and application thereof. Highly branching characteristics of cationic tree-like macromolecular materials are utilized, a large number of Gd3+ is connected onto the surface of the tumor targeting magnetic resonance contrast medium modified by the chlorotoxin, signal intensity of magnetic resonance imaging (MRI) diagnosis is improved, and diagnosis drug dosage is reduced. Besides, tumor targeting head base-chlorotoxin (CTX) extremely having clinical application potential is utilized to modify the cationic tree-like macromolecular materials, gathering of the Gd3+ at the tumor position is improved, MRI signals at the tumor position are enhanced, and sensitivity and accuracy of the tumor diagnosis are improved. Compared with the existing commercial micromolecule gadolinium-class contrast media, the tumor targeting magnetic resonance contrast medium modified by the chlorotoxin is high in relaxation rate, small in dosage and capable of enhancing the MRI signals at the tumor position in a targeting mode, improving signal contrast between the tumor position and normal tissue, effectively prolonging observable time of the MRI signals at the tumor position simultaneously and facilitating accurate tumor diagnosis.

Description

technical field [0001] The invention belongs to the field of biological technology, and relates to the preparation of a chlorinated toxin-modified tumor targeting magnetic resonance contrast agent, its preparation method and application. Background technique [0002] Early diagnosis of tumors and their nature (benign or malignant) is of great significance to the treatment of tumors. At present, the clinical detection of malignant tumors mainly relies on immunobiochemical detection, supplemented by physical means such as computerized tomography (CT) and magnetic resonance imaging (MRI). Although biological histochemical detection has high detection sensitivity and specificity, it requires tissue sections, which can only be limited to in vitro detection and takes a long time. MRI is superior to CT in diagnosing intracranial primary tumors, metastatic tumors, and primary liver cancer. In the prior art, MRI diagnosis is mainly carried out by gadolinium-based contrast agents, b...

Claims

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Application Information

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IPC IPC(8): A61K49/14
Inventor 黄容琴蒋晨韩亮刘书环李剑锋
Owner FUDAN UNIV
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