Preparation method of nuclide molecular probe targeting CD4 receptor and application of nuclide molecular probe serving as heart transplant rejection reaction imaging agent

A molecular probe and receptor technology, applied in the fields of radiochemistry and clinical nuclear medicine, can solve the problems of insufficient image resolution, poor specificity, and low diagnostic sensitivity, and achieve high sensitivity, high specificity, and good affinity.

Pending Publication Date: 2020-05-01
XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In view of the above problems, the present invention provides a preparation method of a radionuclide molecular probe targeting CD4 receptors and its application as an imaging agent for cardiac transplantation rejection, which mainly solves the problem of invasiveness, low diagnostic sensitivity and poor specificity in the prior art. , Insufficient image resolution, etc.

Method used

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  • Preparation method of nuclide molecular probe targeting CD4 receptor and application of nuclide molecular probe serving as heart transplant rejection reaction imaging agent
  • Preparation method of nuclide molecular probe targeting CD4 receptor and application of nuclide molecular probe serving as heart transplant rejection reaction imaging agent
  • Preparation method of nuclide molecular probe targeting CD4 receptor and application of nuclide molecular probe serving as heart transplant rejection reaction imaging agent

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] A.zeba desalting column (Thermo scientific, USA) was used to process CD4 monoclonal antibody:

[0043] 1. Remove the bottom plug and top cap of the desalting column, put it into a 1.5mL centrifuge tube, centrifuge at 1500×g for 1min, and discard the storage solution;

[0044] 2. Add 300 μL 1×modification buffer (modification buffer, Solulink, USA), centrifuge at 1500×g for 1 min, and repeat three times;

[0045] 3. Put the desalting column in a new centrifuge tube, add CD4 monoclonal antibody (150ug, 1nmol) to the center of the resin, centrifuge at 1500×g for 2min, and collect the sample;

[0046] b. 99m Tc-labeled CD4 (leukocyte differentiation antigen 4) monoclonal antibody:

[0047] 1. Weigh SHNH and dissolve it in anhydrous DMSO (dimethyl sulfoxide) (10ug / μL), take 4μL (140nmol) and mix it with the treated antibody, and place it on a shaker at 4°C in the dark to react overnight;

[0048] 2. The reaction product was removed by Zeba desalting column to remove exces...

Embodiment 2

[0078] A. Mix leukocyte differentiation antigen 4 monoclonal antibody with 6-hydrazinonicotinoyl succinimide hydrochloride solution, shake at 4°C and react in the dark;

[0079] 6-hydrazinonicotinoylsuccinimide hydrochloride is dissolved in dimethyl sulfoxide solution to form 6-hydrazinonicotinoylsuccinimide hydrochloride solution,

[0080] The concentration of 6-hydrazinonicotinoylsuccinimide hydrochloride in the 6-hydrazinonicotinoylsuccinimide hydrochloride solution is 10 mg / ml;

[0081] The molar ratio of 6-hydrazinonicotinoylsuccinimide hydrochloride solution to leukocyte differentiation antigen 4 monoclonal antibody is 10:1;

[0082] B. The 6-hydrazinonicotinamide-leukocyte differentiation antigen 4 monoclonal antibody obtained in the extraction reaction,

[0083] C. Mix 6-hydrazinonicotinamide-leukocyte differentiation antigen 4 monoclonal antibody with N-tris(hydroxymethyl)methylglycine, stannous chloride and technetium,

[0084] The concentration of N-tris(hydroxyme...

Embodiment 3

[0089] A. Mix leukocyte differentiation antigen 4 monoclonal antibody with 6-hydrazinonicotinoyl succinimide hydrochloride solution, shake at 5°C and react in the dark;

[0090] 6-hydrazinonicotinoylsuccinimide hydrochloride is dissolved in dimethyl sulfoxide solution to form 6-hydrazinonicotinoylsuccinimide hydrochloride solution,

[0091] The concentration of 6-hydrazinonicotinoylsuccinimide hydrochloride in the 6-hydrazinonicotinoylsuccinimide hydrochloride solution is 20 mg / ml;

[0092] The molar ratio of 6-hydrazinonicotinoylsuccinimide hydrochloride solution to leukocyte differentiation antigen 4 monoclonal antibody is 30:1;

[0093] B. The 6-hydrazinonicotinamide-leukocyte differentiation antigen 4 monoclonal antibody obtained in the extraction reaction,

[0094] C. Mix 6-hydrazinonicotinamide-leukocyte differentiation antigen 4 monoclonal antibody with N-tris(hydroxymethyl)methylglycine, stannous chloride and technetium,

[0095] The concentration of N-tris(hydroxyme...

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Abstract

The invention relates to a preparation method of a nuclide molecular probe targeting a CD4 receptor and an application of the nuclide molecular probe serving as a heart transplant rejection reaction imaging agent. The method comprises the following steps: mixing leukocyte differentiation antigen 4 monoclonal antibody with a 6-hydrazino nicotinoyl succinimide ester hydrochloride solution, performing extraction reaction to obtain 6-hydrazino nicotinamide-leukocyte differentiation antigen 4 monoclonal antibody, mixing the 6-hydrazinonicotinamide-leukocyte differentiation antigen 4 monoclonal antibody with N-tri (hydroxymethyl) methylglycine, stannous chloride and technetium, and performing oscillation reaction; the beneficial effects is as follows: higher marking rate and radiochemical puritycan be obtained, and good affinity to CD4 + T lymphocytes can be obtained; as a transplant rejection reaction imaging agent, the probe has the characteristics of high sensitivity and high specificity, and can realize early diagnosis of acute rejection.

Description

technical field [0001] The invention belongs to the technical fields of radiochemistry and clinical nuclear medicine, and in particular relates to a preparation method and application of a nuclide molecular probe targeting CD4 (leukocyte differentiation antigen 4) receptor. Background technique [0002] Heart transplantation (HT) is an effective means of treating end-stage heart disease. Although the curative effect of immunosuppression is continuously improved, the incidence of acute rejection (AR) is still as high as 40%, and the mortality rate is 12%. It is the most common complication and the main cause of death after heart transplantation. Therefore, it plays an extremely important role in the early diagnosis and monitoring of AR after HT. [0003] However, there is currently no highly specific non-invasive detection technology clinically. Transjugular endomyocardial biopsy (EMB) is the "gold standard" for diagnosing AR after HT. It is useful in diagnosing rejection a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K51/10A61K103/10
CPCA61K51/1027
Inventor 谢明星兰晓莉李慧玲陈逸寒张丽靳巧锋盖永康吴雅
Owner XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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