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18F labelled nano antibody probe, and preparation method and application thereof

A nanobody and 18F technology, applied in the field of nuclear medicine and molecular imaging, can solve the problems of large bone marrow puncture trauma, poor repeatability, false positives, etc., and achieve the effects of wide application range, reduced preparation cost, and accurate detection

Active Publication Date: 2021-10-08
RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, bone marrow puncture is not only traumatic and reproducible, but also sampling errors, tumor heterogeneity and other factors often lead to false negative or false positive biopsy results.

Method used

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  • 18F labelled nano antibody probe, and preparation method and application thereof
  • 18F labelled nano antibody probe, and preparation method and application thereof
  • 18F labelled nano antibody probe, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1 Synthesis of RJDJ01

[0052] Such as figure 1 The synthetic route shown autonomously synthesizes RJDJ01:

[0053] 1. Accurately weigh 1g of tetraethylene glycol (about 5.1mmol), dissolve it in 15mL of dichloromethane, then mix 2g (about 10.5mmol) of p-toluenesulfonyl chloride and 0.59g of potassium hydroxide (about 10.5 mmol) was slowly added to the above mixture and reacted overnight at room temperature. After washing with water, the liquid was separated to obtain 2 g of crude product (yield about 78%).

[0054] 2. The above crude product was dissolved in dichloromethane, then 0.56g (about 4mmol) of 3-hydroxyl-2-nitropyridine and 96mg of sodium chloride (about 4mmol) were added, and after overnight reaction at room temperature, column chromatography separated to obtain 1g (about 2.1 mmol) of 2-(2-(2-(2-((2-nitropyridin-3-yl)oxy)ethoxy)ethoxy)ethoxy)4-methylbenzenesulfonate Acetate ethyl ester, the yield is about 51%.

[0055] 3.940 mg (about 2 mmol) of 2...

Embodiment 2

[0057] Embodiment 2 Click chemical reaction substrate 1 18 Automated preparation of F[F]-RJDJ01

[0058] The specific experimental scheme is as follows: Weigh 2–2.5 mg RJDJ01, dissolve it in 1 mL dimethyl sulfoxide (DMSO); transfer 18F-fluoride (33.49–39.39 GBq) with a pre-balanced anion exchange Potassium carbonate (3mg) and 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane (15mg) were used as the mobile phase to wash the anion exchange column; after the solvent was evaporated to dryness, add RJDJ01 dissolved in 1mL DMSO; the reaction system was heated at 120°C for 14 minutes; 3mL sterilized water for injection was added to the reaction system, the reaction system was transferred to a C18 column, and the mobile phase was set to 0.1% trifluoroacetic acid containing 32% acetonitrile ( trifluoroacetic acid), set the flow rate to 4.6mL / min, purified by HPLC, collected 18 F-RJDJ01 to the pear-shaped bottle; add 10mL sterile water for injection to the pear-shaped bottle ...

Embodiment 3

[0059] Example 3 Preparation of click chemical reaction substrate DBCO-MM01, and preparation of novel CD38-specific nanobody probes by click chemical reaction 18 F[F]-MM01

[0060] The reaction principle is as Figure 5 18 As shown in the schematic diagram of F randomly labeled nanobody, the click chemical reaction substrate DBCO-MM01 was prepared, and the novel CD38-specific nanobody probe was prepared through the click chemical reaction 18 F[F]-MM01.

[0061] DBCO-NHS ester (CAS#:1353016-71-3, MeloPEG) was randomly coupled with MM01 to prepare the click chemistry reaction substrate DBCO-MM01. The specific steps are as follows: Dissolve 1 mg of CD38-specific nanobody MM01 in phosphate buffered saline (PBS) with a volume of about 1 mL, add 80–100 μL of 0.1M sodium carbonate (Na2CO3) buffer to adjust the pH of the nanobody solution to 9.0–10. DBCO-NHS ester freshly dissolved in dimethyl sulfoxide (DMSO) was added to the Nanobody solution at a DBCO-NHS ester / MM01 molar ratio...

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Abstract

The invention discloses an 18F labelled nano antibody probe, and a preparation method and application thereof, and relates to the field of nuclear medicine and molecular imaging; a targeting carrier of the probe comprises a nano antibody MM01, a nano antibody MM02 or a derivative of the nano antibody MM02; and the preparation method comprises the following steps of: synthesizing a small molecule compound precursor RJDJ01; preparing an 18F labelled precursor 18F[F]-RJDJ01; and preparing a fluorine-18(18F) labelled nano antibody probe through a click chemical reaction, wherein the probe is used for detecting the multiple myeloma CD38 specific nano antibody. According to the invention, by creating a novel CD38 specific nano antibody probe 18F[F]-MM01, noninvasive visualization of CD38 expression is realized; and noninvasive detection of multiple myeloma is realized. The probe has the advantages of simple preparation process, low cost, high specificity, high stability, short imaging period, low radiation dosage, easiness in clinical transformation and the like.

Description

technical field [0001] The invention relates to the fields of nuclear medicine and molecular imaging, in particular to a 18 F-labeled nanobody probe, its preparation method and application. Background technique [0002] In 1993, Belgian scientist Hamers et al reported for the first time in the journal "Nature" that there is an antibody that naturally lacks light chains in the peripheral blood of alpacas (Nature.1993; 363(6428):446-8.), which has a special Antibodies of the domain are heavy-chain antibodies (Heavy-chain antibodies, HCAbs). By means of molecular biology, the variable region of the heavy chain antibody can be cloned to obtain an antigen-binding fragment with only the variable region of the heavy chain, which is a nanobody (VHH, Variable Domain of Heavy Chain of Heavy Chain Antibody). VHH crystals are 2.5nm wide, 4nm long, and have a molecular weight of only 15KDa, so they are also called nanobodies ( Ablynx company registered trade name). Nanobodies are cu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K51/10A61K51/08A61K51/06A61K51/04C07D213/65A61K101/02
CPCA61K51/10A61K51/08A61K51/06A61K51/0455C07D213/65C07B2200/05
Inventor 魏伟军王成刘建军
Owner RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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