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Malignant lymphoma radioactive target molecule imaging agent and/or target therapeutic agent

A targeted therapeutic agent and targeted molecular technology, which is applied in the direction of radioactive carriers, antineoplastic drugs, drug combinations, etc. In order to achieve the effects of enriching theory and clinical practice, improving penetrating power, and convenient and easy preparation

Inactive Publication Date: 2010-08-11
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] Therefore, the current difficulty faced by immunoimaging agents or therapeutic agents is that when the molecular weight of the antibody fragment is small, it has a strong penetrating power to the tumor, but if the molecular weight is less than the renal clearance threshold (60kD ~ 80kD), it is easy to be cleared, and the tumor tissue However, when the molecular weight of the antibody is greater than the renal clearance threshold (60kD-80kD), although it is not easy to be cleared, the non-specific uptake of the liver and spleen is high, resulting in significant The image background is high, which interferes with the diagnosis results. At the same time, it is difficult for antibodies with large molecular weight to penetrate the tumor, and the tumor site takes up less imaging agent or therapeutic agent, so that effective concentration cannot be formed, so the tumor imaging or treatment effect is not good.
[0012] For tumors caused by Epstein-Barr virus, such as malignant lymphoma, although there are a variety of technical methods that can be used to diagnose malignant lymphoma clinically, there are no relevant reports on specific targeted molecular imaging technology for malignant lymphoma

Method used

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  • Malignant lymphoma radioactive target molecule imaging agent and/or target therapeutic agent
  • Malignant lymphoma radioactive target molecule imaging agent and/or target therapeutic agent
  • Malignant lymphoma radioactive target molecule imaging agent and/or target therapeutic agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1 Preparation of Small Molecule Fusion Peptide

[0049]According to Qiu Xiaoqing et al. in the literature (Xiao-Qing Qiu, He Wang, Bei Cai, Lan-Lan Wang&Shi-Tao Yue. Small antibody mimetics comprising two complementarity-determining regions and a framework region for tumor targeting. NATURE BIOTECHNOLOGY, 2007: 25(8) : 921-928) prepared small molecule fusion peptide, or synthesized by Xi'an Lianmei Biological Products Co., Ltd. according to the amino acid sequence disclosed in SEQ ID NO.1-SEQ ID NO.5.

Embodiment 2

[0050] Embodiment 2 prepares imaging agent of the present invention

[0051] 1.1 Materials

[0052] 28P (SEQ ID NO.1) was synthesized by Xi'an Lianmei Biological Products Co., Ltd. with a purity of >95% (see figure 1 ).

[0053] Use 24 BALB / c mice, body weight about 20g, male or female, be divided into 7 groups, 5 in each group (provided by Experimental Animal Center of Sichuan University); 125 I / Na 131 I is produced by Chengdu Zhonghe Qualcomm Isotope Co., Ltd. (no carrier, no reducing agent, radiochemical purity ≥ 96%, pH value 7.0~8.0, gamma impurity < 0.1%); N-bromosuccinimide is a sigma product ( USA), HAS (Shanghai), analytically pure; acetone (Chengdu Xinchuan Chemical Reagent Co., Ltd.), gamma counter (state-owned 262 factory), ESJ120-4 electronic analytical balance (Shenyang), vortex mixer XW-80A ( Shanghai Medical University).

[0054] 2.1 28P 125 I labeling and determination of optimal labeling conditions

[0055] N-bromosuccinimide (NBS) was used as an oxida...

Embodiment 3

[0094] Example 3 Detection of distribution of iodine-125 labeled 28P in normal mice

[0095] Preparation of iodine-125 labeled 28P: take 10 μl Na 125 I (about 1.5mCi), then add 10μl (1μg / μl) NBS solution, then add pre-packed 1μg / μl 28P, and finally add 100μl 0.05mol / L PBS buffer (pH7.2~7.4) and mix well. Shake and mix slowly, react for 3 minutes, add 50 μl of 2% HSA solution to terminate the reaction for 30 seconds, and labeling is completed. Paper chromatography measures the labeling rate, the stationary phase is Xinhua No. I paper, and the developer is acetone: normal saline=1: 1 (volume ratio), 125 Rf of I-28P=0.4~0.6, free 125 The Rf of I was 0.8-1.0, and the labeling rate was identified by TLC scanner. acquired 131 The radiochemical purity of I-28P is 96.8%.

[0096] 125 Biodistribution of I-28P marker in normal mice Thirty-five healthy Kunming mice were selected and randomly divided into 7 groups with 5 mice in each group. Each mouse was injected via the tail vein...

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Abstract

The invention discloses an application of fusion peptide in the preparation of malignant lymphoma radioactive target molecule imaging agent and / or radioactive target therapeutic agent and a radioactive target molecule imaging agent and / or target therapeutic agent. The fusion peptide is obtained by connecting the framework region 2 (VHFR2 or VLFR2) of a monoclonal antibody heavy-chain variable domain (or light-chain variable domain) with the complementary determining region 1 or 3 (VHCDR1 or VHCDR3) of a heavy-chain variable domain and the complementary determining region 1 or 3 (VLCDR1 or VLCDR3) of a light-chain variable domain, the molecular weight of the fusion peptide is 3-4kDa, the monoclonal antibody is a monoclonal antibody for identifying EB virus surface antigen g p 350 / 220 antigenic determinant, and the tumor is malignant tumor caused by the EB virus. The radioactive immune-imaging agent or therapeutic agent prepared in the invention has the advantages of small molecular weight, high tumor penetrating power, good targeting, high tumor accumulation, fast removing performance in blood, no obvious radioactive distribution in non-target organs away from tumor such as the liver and spleen, no immunogenicity, safety and the like.

Description

technical field [0001] The present invention relates to a radioactive targeted molecular imaging agent and / or a new drug for radioactive targeted therapy, in particular to a radionuclide-labeled small molecule peptide tumor targeted molecular imaging agent and / or a new therapeutic drug and its preparation method and Applications in tumor-targeted molecular diagnosis and / or targeted therapy. Background technique [0002] Currently, antibody-based targeted therapy has achieved unprecedented success. The US FDA has approved 22 monoclonal antibodies (monoclonal antibody, mAb) for clinical use, and hundreds of monoclonal antibodies are being used in preclinical research for the treatment of cancer, immune system diseases and infectious diseases. Revenues for the top five therapeutic antibodies (Rituxan, Remicade, Herceptin, Humira, and Avastin) nearly doubled from $6.4 billion in 2004 to $11.7 billion in 2006. These therapeutic and commercial successes reflect the significant a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K51/10A61P35/00A61K103/32A61K103/30A61K103/20A61K103/10A61K103/00A61K101/02A61K101/00
Inventor 范成中解朋邓候富李林梁正路匡安仁谭天秩
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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