Nuclide marked trastuzumab monoclonal antibody as well as preparation method and application thereof

A trastuzumab and labeling technology, applied in the field of nuclear medicine, can solve problems such as drug resistance and recurrence, and achieve stable properties, low systemic background, and good imaging effects

Inactive Publication Date: 2020-03-31
BEIJING CANCER HOSPITAL PEKING UNIV CANCER HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In addition, there are problems of recurrence and drug resistance in the process of targeted therapy, so the realization of

Method used

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  • Nuclide marked trastuzumab monoclonal antibody as well as preparation method and application thereof
  • Nuclide marked trastuzumab monoclonal antibody as well as preparation method and application thereof
  • Nuclide marked trastuzumab monoclonal antibody as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1 New nuclide 124 Preparation of I-labeled Trastuzumab

[0027] 124 I-Trastuzumab is prepared by NBS reaction: to 0.7Ml (45KBq / μL) Na 124 Add 0.5ml 0.1M PB (pH7.2) buffer, 0.1mL (10mg / mL) Trastuzumab monoclonal antibody solution (prepared with water for monoclonal antibody solution) and 12μg NBS to the I solution in sequence. React at 37°C for 60 seconds, and add 10% HSA to terminate the reaction. After the reaction solution is purified by PD-10 column, the target product is obtained 124 I-Trastuzumab.

[0028] The labeling rate is greater than 95%. After purification with a PD-10 pre-packed gel column, the radiochemical purity of the target compound is greater than 99%. Before use, the PD-10 column needs to be equilibrated with 0.01M pH 7.4PBS, adding 5 mL each time, draining by gravity flow rate, and repeating 5 times. Then use 0.01M pH 7.4PBS to purify the target compound.

[0029] Radio-TLC and Radio-HPLC were used to determine the labeling rate and radiochemica...

Embodiment 2124I

[0030] Example 2 124 In vitro stability analysis of I-Trastuzumab labeled compounds

[0031] Stability in 0.01M pH 7.4PBS solution: take 10μL of purified radioactivity containing 37-74kBq (1-2μCi) 124 I-Trastuzumab was added to the 7.4PBS solution and incubated at 4℃ for 2h, 24h, 48h, 72h and 96h. Take out 2μL of the sample and mix it with 20ul of saturated EDTA. Take 2μL of the sample to be tested and drop it on the No. 1 filter paper from Xinhua Place the bottom 1cm in a physiological saline expansion system. After it is fully expanded, take out the filter paper and dry it for radio-TLC detection.

[0032] Stability in 5% HSA solution: Take 10μL of purified radioactivity containing 37-74kBq (1-2μCi) 124 I-Trastuzumab was added to 100ul of 5% HSA solution, and after incubating at 4℃ for 2h, 24h, 48h, 72h and 96h, 2μL of the sample was taken out and mixed with 20ul of saturated EDTA, and 2μL of the sample to be tested was dropped on Xinhuayi 1cm at the bottom of the No. filter pape...

Embodiment 3124I

[0034] Example 3 124 Study on PET imaging of I-Trastuzumab labeled compound in animals

[0035] Take 10 HER2-positive PDX models of gastric cancer randomly divided into 124 I-Trastuzumab positive group and 124 I-hIgG1 positive group, prepare 5 HER2-negative PDX models of gastric cancer (female, 5-6 weeks old, 18-20g, right inguinal area, tumor diameter up to 1cm), 124 I-Trastuzumab positive group and 124 I-Trastuzumab negative group was injected with 18.5MBq (0.5mCi, 200μL) via tail vein 124 I-Trastuzumab, 124 I-hIgG1 positive group was injected with 18.5MBq (0.5mCi, 200μL) via tail vein 124 I-hIgG1. Each PDX model in each group was subjected to Micro-PET imaging studies at 2h, 24h, 48h, 72h and 96h after injection; before imaging, nude mice were placed in the Summit AS-1-000-7 small animal anesthesia system at 3L / min. The mice are anesthetized with halothane gas, the PDX model is fixed in the center of the Micro-PET scanning bed in a prone position, and the mice are scanned in a ...

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Abstract

The invention provides a nuclide marked trastuzumab monoclonal antibody as well as a preparation method and application thereof. Through radionuclide 124I marking, a corresponding radioactive moleculeprobe 124I-Trastuzumab is obtained and is combined with HER2, so that tumor tissue with high expression of HER2 can be accurately positioned by nuclear medicine means, and the purposes of disease targeted molecule image diagnosis and treatment can be achieved.

Description

Technical field [0001] The invention relates to the field of nuclear medicine, in particular to a nuclide-labeled trastuzumab and a preparation method and application thereof. Background technique [0002] With the in-depth development and fusion of nuclear medicine and molecular biology, medical imaging technology has entered the era of molecular imaging, in which Positron Emission Tomography (PET) for functional imaging enables people to truly understand the molecular level Began to recognize and diagnose diseases, especially in the diagnosis and treatment of tumors. By tracing the changes of receptors in diseased tissues and abnormal cell signal transduction, it can overcome the shortcomings of modern diagnostic technology, provide basis for early diagnosis, clinical staging, and efficacy evaluation of tumors, and evaluate the prognosis. It can also be applied Targeted therapy for tumors. In addition to multi-modal imaging equipment with high resolution, high sensitivity, an...

Claims

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Application Information

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IPC IPC(8): A61K51/10A61P35/00A61K101/02
CPCA61K51/103A61P35/00
Inventor 杨志郭晓轶朱华周妮娜刘特立夏雷
Owner BEIJING CANCER HOSPITAL PEKING UNIV CANCER HOSPITAL
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