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HER2 targeting affinitybody and application thereof

A RESCA-HER2-BCH, targeted technology, applied in the field of radiochemistry, clinical nuclear medicine, and organic chemistry, can solve the problems of high blood pool and liver background, long half-life, slow blood pharmacokinetics, etc. Effects of renal toxicity, rapid renal metabolism, and good in vivo stability

Inactive Publication Date: 2022-02-22
BEIJING CANCER HOSPITAL PEKING UNIV CANCER HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the blood pharmacokinetics of the intact antibody is relatively slow, requiring radionuclide labeling with a relatively long half-life, and high background in the blood pool and liver. In order to obtain better image contrast, imaging at a longer time point is required ( 64 The best imaging time of Cu-trastuzumab is 1-2 days, 89 The best imaging time of Zr-trastuzumab is marked 4-6 days)

Method used

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  • HER2 targeting affinitybody and application thereof
  • HER2 targeting affinitybody and application thereof
  • HER2 targeting affinitybody and application thereof

Examples

Experimental program
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Effect test

preparation example Construction

[0038] 68 The preparation method of Ga-RESCA-HER2-BCH includes: taking 1 mL of 0.05 M HCl solution for washing 68 Add Ga to 65 μl 1M NaAc; add 10 μl 10 mg / ml RESCA-HER2-BCH precursor to the above system, mix well, 90±5 o C reaction for 10-15 min, when the labeling rate is less than 90%, use Sep-pak C18 Column to separate and purify, wherein the Sep-pak column needs to be activated with 5 mL of absolute ethanol and 5 mL of high-purity water for backup, and 3.0-5.0 mL of normal saline Elute radioactive impurities, and then elute the target compound with 0.6±0.1 mL 80% ethanol 68 Ga-RESCA-HER2-BCH, using radio-HPLC or radio-TLC to determine the labeling rate and radiochemical purity.

[0039] Made 68 The radiochemical purity of Ga-RESCA-HER2-BCH after isolation and purification is greater than 99%.

[0040] 18 The preparation method of F-RESCA-HER2-BCH comprises: the accelerator production containing 18 f - H 2 18 O through the QMA ion exchange column, the 18 f - Adsor...

Embodiment 1

[0048] Example 1 Preparation of Affibody RESCA-HER2-BCH Targeting HER2

[0049] Preparation of RESCA-(AEEA)-VDNKFNKEMRNAYWEIALPNLNNQQKRAFIRSLYDDPSQSANLLAEAKKLNDAQAPK[(Acp)-(Acp)] was obtained by solid phase synthesis.

[0050] 1. resin swelling

[0051] Put 2-Chlorotrityl Chloride Resin into the reaction tube, add DCM (15ml / g), and shake for 30min.

[0052] 2. first amino acid

[0053] Filter the solvent through the sand core, add 3 times molar excess of Fmoc-L-Lys(Dde)-OH, add DMF to dissolve, then add 10 times molar excess of DIEA (N,N-diisopropylethylamine), Shake for 60min. Block with methanol.

[0054] 3. Deprotection

[0055] Remove DMF, add 20% piperidine DMF solution (15ml / g), shake for 5min, remove and add 20% piperidine DMF solution (15ml / g), shake for 15min.

[0056] 4. detection

[0057] Take out the piperidine solution, take more than a dozen resins, wash them three times with ethanol, add detection reagents for detection, heat at 105°C-110°C for 5min, ...

Embodiment 268G

[0084] Example 2 68 Preparation of Ga-RESCA-HER2-BCH

[0085] The RESCA-HER2-BCH prepared in Example 1 is subjected to nuclide 68 Ga(T 1 / 2 =68 min; β + :89%; E=511keV) marks, 68 For Ga 68 Ge- 68 Ga generators are prepared. Take 1 mL of 0.05 M HCl solution to rinse 68 Add Ga to 65 μl 1M NaAc; add 10 μl 10 mg / ml RESCA-HER2-BCH precursor (water-soluble) to the above system, mix well, 90±5 o C was reacted for 10-15 min. When the labeling rate was less than 90%, it was separated and purified with Sep-pak C18 Column to obtain 68 Ga-RESCA-HER2-BCH. preferred 68The radiochemical purity of Ga-RESCA-HER2-BCH is greater than 99%. Take an appropriate amount of sterile-filtered product preparations for quality control inspection, and carry out follow-up research after all items are qualified.

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Abstract

The invention provides an HER2 targeting affinitybody and application thereof. The HER2 targeting affinity RESCA-HER2-BCH is characterized in that the structure of the HER2 targeting affinity RESCA-HER2-BCH is RESCA-(AEEA)-VDNKFNKEMRNAYWEIALLPNLNNQQKRAFIRSLYDDPSQSANLLAEAKKLNDAQAPK[(Acp)-(Acp)]. According to the invention, RESCA-HER2-BCH is subjected to diagnostic and therapeutic radionuclide labeling and evaluation, so that the RESCA-HER2-BCH is expected to be used for diagnosis and treatment of HER2 positive tumors such as HER2 positive breast cancer, gastric cancer, cervical cancer, prostatic cancer, lung cancer and the like.

Description

technical field [0001] The invention relates to the technical fields of organic chemistry, radiochemistry and clinical nuclear medicine, in particular to an affibody targeting HER2 and its application. Background technique [0002] With the in-depth development and integration of nuclear medicine and molecular biology, medical imaging technology has entered the era of molecular imaging, in which Positron Emission Tomography (PET) for functional Begin to recognize and diagnose diseases, especially highlight its advantages in the diagnosis and treatment of tumors. By tracking the changes of receptors in diseased tissues and the abnormality of cell signal transduction, it can overcome the defects in modern diagnostic techniques, provide the basis for early diagnosis of tumors, clinical staging, and curative effect evaluation, and evaluate the prognosis. Targeted therapy for tumors. Tumor radioimmunoimaging is to inject specific antibodies against tumor-associated antigens or ...

Claims

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Application Information

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IPC IPC(8): C07K14/31C07K1/13A61K51/08A61P35/00
CPCC07K14/31A61K51/08A61P35/00
Inventor 杨志郭晓轶朱华刘特立周妮娜刘福涛
Owner BEIJING CANCER HOSPITAL PEKING UNIV CANCER HOSPITAL