A radioactive complex targeting HER2 and its preparation method and application

A complex and radioactive labeling technology, applied in the direction of radioactive physical shape, radioactive carrier, drug delivery, etc., can solve the problems of long residence time and high concentration, and achieve reduced radiation dose, high clinical promotion value, excellent imaging or treatment effect of effect

Active Publication Date: 2021-12-21
SHANGHAI THERANOSTICS BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although 68 Ga-ABY-025 has an excellent tumor imaging effect, but because Affibody is mainly excreted by the kidney and the metabolites can be reabsorbed by the renal tubules, the concentration of radioactivity in the kidney is abnormally high and the residence time is particularly long

Method used

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  • A radioactive complex targeting HER2 and its preparation method and application
  • A radioactive complex targeting HER2 and its preparation method and application
  • A radioactive complex targeting HER2 and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Prepare a polypeptide compound with HER2 targeting function, and its synthetic route is as follows:

[0059]

[0060] Concrete preparation process comprises the following steps:

[0061] 1. Synthesis of compound 1:

[0062] Add 0.5g Fmoc-Lys(Dde)-Resin (the amount of substance of Fmoc-Lys(Dde)-OH is 0.4mmol, 1 equivalent) in solid-phase synthesizer, take DMF as reaction solvent, with 0.8M DIPEA / DMF and 0.4M HBTU / DMF were used as activators, and 20% piperidine in DMF was used as the eluent of Fmoc. According to the sequence of the polypeptide, Fmaoc-Val-OH (0.543g, 4 equivalents) and Boc-Met were added sequentially. -OH (0.399 g, 4 equivalents) to extend the peptide chain. After the solid-phase synthesis, the crude polypeptide product attached to the resin was placed in 3 mL of 2% hydrazine hydrate in DMF, stirred at room temperature for 1.5 h, filtered with suction, and the resin was washed with dichloromethane, methanol and DMF in sequence. The resin was then pl...

Embodiment 2

[0070] Prepare another polypeptide compound with HER2 targeting function, and its synthetic route is as follows:

[0071]

[0072] Concrete preparation process comprises the following steps:

[0073] 1. Synthesis of compound 1:

[0074]Add 0.5g Fmoc-Lys(Dde)-Resin (the amount of substance of Fmoc-Lys(Dde)-OH is 0.4mmol, 1 equivalent) in solid-phase synthesizer, take DMF as reaction solvent, with 0.8M DIPEA / DMF and 0.4M HBTU / DMF were used as activators, and 20% piperidine in DMF was used as the eluent of Fmoc. According to the sequence of the polypeptide, Fmaoc-Val-OH (0.543g, 4 equivalents) and Boc-Met were added sequentially. -OH (0.399 g, 4 equivalents) to extend the peptide chain. After the solid-phase synthesis, the crude polypeptide product attached to the resin was placed in 3 mL of 2% hydrazine hydrate in DMF, stirred at room temperature for 1.5 h, filtered with suction, and the resin was washed with dichloromethane, methanol and DMF in sequence. The resin was th...

Embodiment 3

[0082] Preparation of lyophilized kits for radiolabelling

[0083] 1) Preparation of lyophilized kits for radioactive Ga-68 and Cu-64 labeling (take the preparation of 100 tubes as an example)

[0084] Weigh 4 mg of compound 4 prepared in Example 1 and dissolve it in 10 mL of 0.5 mol / L acetic acid-sodium acetate buffer solution (pH=4). After sterile filtration, it is divided into 100 cryopreservation tubes, and then placed in the freezer. Freeze-dry in a desiccant for 24 hours, and seal with a stopper to obtain a freeze-dried medicine box I. According to the formation of the freeze-dried powder injection of the kit, excipients such as mannitol and ascorbic acid can be added to the kit, and the dosage of compound 4 and excipients can be adjusted to optimize the molding of the kit.

[0085] 2) Preparation of freeze-dried kits for radioactive F-18 labeling (taking the preparation of 100 tubes as an example)

[0086] Weigh 4 mg of the compound 4 prepared in Example 1 and dissolv...

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Abstract

The present invention provides a polypeptide compound with HER2 targeting function, which is composed of a HER2 affinity body and a bifunctional chelating agent connected through a polypeptide sequence; the polypeptide sequence is Met-Val-Lys; the polypeptide compound has a general structure The formula is shown in the following formula (I), wherein, R is a HER2 affinity body molecule, and X is a bifunctional chelating agent group. The present invention also provides a HER2-targeted radiolabeled complex using the polypeptide compound as a ligand. The radiolabeled complexes of the present invention can be used as radioactive diagnostic probes for the evaluation of HER2 receptors in breast cancer. The probes can reduce kidney accumulation while keeping tumor uptake unchanged, thereby improving tumor target and HER2 receptors. Non-target ratio, while reducing the radiation dose to the kidney. The present invention also provides the preparation method of the polypeptide compound and radiolabeled complex, and its application in the preparation of HER2-positive breast cancer radiodiagnostic and therapeutic probes for humans or animals.

Description

technical field [0001] The invention relates to a radioactive complex, in particular to a radioactive complex targeting HER2, its preparation method and its application as a diagnosis and treatment probe. Background technique [0002] According to data from the International Cancer Research Center, the age-standardized incidence rate of breast cancer in the world (43.1 / 100,000 people) ranked first among female cancers in 2012, far ahead of the second-ranked colorectal cancer (14.3 / 100,000 people) human), accounted for 35.3% of new tumors in women, and accounted for 20.8% of all cancer deaths in women. According to data from the National Cancer Center of China, in 2015 breast cancer was still the cancer with the highest incidence rate among women, and it was also the second leading cause of cancer death among women after lung cancer. Breast cancer has become a major public health problem in the current society, and the key to improving the efficacy of breast cancer lies in e...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K51/08A61K51/12
CPCA61K51/08A61K51/1241A61K51/121
Inventor 陈小元张明如
Owner SHANGHAI THERANOSTICS BIOTECH CO LTD
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