Gd-DTPA-Polylysine-McAb junctional complex, preparation method and application thereof

A combination of monoclonal antibody technology, applied in the field of combination, can solve the problems of non-targeting, inability to accurately distinguish benign and malignant lesions, and difficulty in early diagnosis of diseases

Inactive Publication Date: 2009-10-28
RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

It has certain value in disease diagnosis. However, magnetic resonance imaging using non-specific contrast agents cannot accurately distinguish between benign and m

Method used

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  • Gd-DTPA-Polylysine-McAb junctional complex, preparation method and application thereof
  • Gd-DTPA-Polylysine-McAb junctional complex, preparation method and application thereof
  • Gd-DTPA-Polylysine-McAb junctional complex, preparation method and application thereof

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Experimental program
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Effect test

Embodiment 1

[0039] Preparation of a Gd-DTPA-Polylysine-McAb (anti-VEGF) conjugate

[0040] I. Synthesis of DTPA bis-anhydride (CaDTPA): 10g of diethylenetriaminepentacid (DTPA) was suspended in a mixture of 30ml of acetic anhydride and 15ml of pyridine, stirred and reacted at 60°C for 6h, after cooling, add an appropriate amount of ethanol to filter, and wash with ether , and dried to obtain a white solid DTPA bisanhydride (CaDTPA) crude product. After recrystallization, it is determined that the melting point of the product is 178~180°C (decomposition), and it has 1845, 1785 cm in the infrared spectrum. -1 C=O stretching vibration doublets of cyclic anhydrides.

[0041] II. Preparation of DTPA-Polysine: weigh Polylysine (polylysine) 10mg, dissolve in 3ml of 0.2mol / L NaH 2 CO 3 / Na 2 HCO 3 DTPA bis-anhydride (CaDTPA) solution was added in the buffer solution (PH=9.6) under constant stirring in an ice bath, and stirred at room temperature for 16 hours to complete the reaction. The re...

Embodiment 2

[0049] Experiment of Gd-DTPA-polylysine-McAb (anti-VEGF monoclonal antibody) in vivo MR molecular imaging of nude mouse model bearing human breast cancer

[0050] Materials and Methods

[0051] 1. Preparation of animal models

[0052] In this experiment, the cell suspension method was used to inoculate the human breast cancer cell line MDA-MB-231 in situ to make a nude mouse model of breast cancer. Nude mice and breast cancer MDA-MB-231 cell lines were purchased from the Cancer Institute of the Chinese Academy of Sciences. The 12 nude mice were all 5-week-old female specific pathogen-free (SPF) BALB / c nude mice, with a mass of 18-20 g. Breast cancer MDA-MB-231 cells were cultured with Leibovitz's L-15medimu (GIBCO) adding 15% fetal bovine serum (GIBCO). 7 / 0.2ml / only inoculated into the fat pad of the second pair of mammary glands on the right side of nude mice. After inoculation, the tumor growth was observed at least three times a week. After 2 weeks, a visible tumor was ...

Embodiment 3

[0075] Control experiment of Gd-DTPA-polylysine-McAb (anti-VEGF monoclonal antibody) and Gd-DTPA in MR molecular imaging of nude mouse model of breast cancer

[0076] At present, the incidence of breast cancer at home and abroad is showing a significant upward trend. The incidence of female breast cancer in many large cities in my country has ranked first in female malignant tumors, and the age of onset tends to be earlier. The diagnosis of breast cancer mainly relies on imaging examinations, including X-ray, B-ultrasound and MRI, etc. Among them, high-field-strength MRI dynamic multi-phase enhanced scanning has the greatest value, and its specificity and sensitivity are high. When extensive Gd-DTPA is present, the MRI findings of breast benign and malignant tumors overlap and cross each other. Therefore, specific diagnosis cannot be achieved, which not only affects the identification of breast cancer and benign lesions, but also affects the detection of early breast cancer. ...

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Abstract

The invention relates to a junctional complex, in particular to a Gd-DTPA-Polylysine-McAb (anti VEGF) juncitonal complex, a preparation method and the application thereof. The Gd-DTPA-Polylysine-McAb (anti VEGF) juncitonal complex (contrast agent) is prepared by the following methods: a, synthesis of DTPA bisanhydride; b, preparation of DTPA-Polylysine; c, preparation of Gd-DTPA-Polylysine; and d, junction of anti VEGF monoclonal antibody and the Gd-DTPA-Polylysine. With the aid of the expansion effect of Polylysine and the specificity of monoclonal antibody, the contrast agent Gd-DTPA-Polylysine-McAb (anti VEGF monoclonal antibody) has the advantages of high immune activity, good targeting ability, high content of Gd, and the like.

Description

technical field [0001] The invention relates to a combination body, in particular to a Gd-DTPA-Polysine-McAb (anti-VEGF) combination body, a preparation method and an application thereof. Background technique [0002] At present, the magnetic resonance contrast agent Gd-DTPA (composed of diethylenetriaminepentaacetic acid (DTPA) and Gd +3 Chelates), which belong to the extracellular space contrast agent, have no specificity. Its enhancement principle is to contain gadolinium (Gd +3 ) The contrast agent enters the artery and is distributed to the tissue structure rich in blood supply along with the blood flow, and quickly returns to the vein, and finally excreted through the kidneys. Gadolinium agents can significantly shorten the T1 time of the distribution area tissue, resulting in a significant increase in signal intensity on T1WI, which is the so-called enhancement. Gd-DTPA is widely used in the MR imaging of multiple systems of the whole body, for example, the diagnos...

Claims

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Application Information

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IPC IPC(8): A61K49/16
Inventor 汪登斌钟高仁龚英陈克敏
Owner RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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