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Novel molecular imaging probe for diagnosing malignant colorectal tumor

A technology for colorectal tumors and molecular imaging, which is applied in the field of biotechnology and molecular imaging, can solve the problems that it is difficult to meet the needs of PET/CT molecular imaging, nuclide modification cannot achieve tumor enrichment, and imaging effects are not ideal, so as to achieve easy-to-clinical Effects of transformation, improvement of in vivo stability, and prolongation of blood circulation time

Pending Publication Date: 2022-05-06
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

At present, a series of animal-level explorations have been carried out for this probe, but poor in vivo stability and rapid metabolism lead to unsatisfactory imaging results
Traditional nucleic acid aptamers have poor in vivo stability and short cycle time, making it difficult to meet the needs of PET / CT molecular imaging
Nuclide modification with a short half-life cannot achieve efficient tumor enrichment, and the imaging target is relatively poor

Method used

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  • Novel molecular imaging probe for diagnosing malignant colorectal tumor
  • Novel molecular imaging probe for diagnosing malignant colorectal tumor
  • Novel molecular imaging probe for diagnosing malignant colorectal tumor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] A preparation of a nucleic acid aptamer molecular probe modified with a trifluoromethyl structural unit, specifically comprising the following steps:

[0067] (1) if figure 1 As shown in the schematic diagram of the preparation method of the nucleic acid aptamer modified by the trifluoromethyl structural unit, the trifluoromethyl group is modified at both ends of the nucleic acid aptamer SGC8 by solid-phase synthesis, and simultaneously introduced into the 5' end of the nucleic acid aptamer The thiol group was used for further coupling, and the non-modified SGC8 nucleic acid aptamer was synthesized for control, and the specific sequence is as follows;

[0068] F-SGC8: 5’-(SH)-FFA TCT AAC TGC TGC GCC GCC GGG AAA ATA CTG TAC GGTTAG AFF-3’

[0069] SGC8: 5'-(SH)-ATC TAA CTG CTG CGC CGC CGG GAA AAT ACT GTA CGG TTA GA-3';

[0070] (2) if figure 2 As shown in the schematic diagram of the coupling of nucleic acid molecules and DFO ligands, 3 mg of DNA-SH synthesized in ste...

Embodiment 2

[0074]A tumor-bearing mouse model of PTK7 positive colorectal cancer was constructed. Specifically include the following steps:

[0075] (1) Use the PTK7-positive colorectal cancer tumor cell HCT116 cell line determined by Western blot to subculture in advance;

[0076] (2) The cultured HCT116 tumor cells were digested and resuspended in the cell culture medium, then mixed with Matrigel (Corning) at a ratio of 1:1, and the mixed cell suspension was placed on ice, Carry out tumor transplantation as soon as possible;

[0077] (3) Take 100 μl of the cell suspension in step 2 (which contains 2×10 6 cells), injected into the right axilla of 4–5 week old Balb / c nude mice (Victoria Lihua) to establish a subcutaneous xenograft tumor model.

Embodiment 3

[0079] Trifluoromethyl structure unit modified SGC8 nucleic acid aptamer ([ 89 Zr]DFO-SGC8-F) PET / CT molecular imaging of subcutaneous colorectal cancer. Specifically include the following steps:

[0080] (1) Inject 3.7–7.4 MBq into each tumor-bearing nude mouse via the tail vein[ 89 Zr]DFO-SGC8-F molecular probe (3–6 per group);

[0081] (2) At specific time points (3 days, 5 days and 7 days) after injection, use isoflurane (concentration: 3%) mixed with oxygen to anesthetize tumor-bearing nude mice, and put the nude mice into a state of deep anesthesia Place on the IRIS small animal PET / CT scanning bed in a prone position, continue to acquire PET and CT images, and use the software that comes with the IRIS system to complete image reconstruction. Such as Figure 7 as shown, 89 Zr labeled SGC8 aptamer ([ 89 Zr]DFO-SGC8) and trifluoromethyl structural unit modified SGC8 nucleic acid aptamer ([ 89 Zr]DFO-SGC8-F) PET / CT molecular images of tumor-bearing mice 3 days after ...

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Abstract

The invention discloses a novel molecular imaging probe for diagnosing malignant colorectal tumor, and relates to the field of biotechnology and molecular imaging, the novel molecular imaging probe is a compound composed of a modified aptamer, a nuclide chelating ligand and nuclide for marking; the modified nucleic acid aptamer is coupled with the nuclide chelating ligand, and then is labeled by the nuclide for labeling; the modified nucleic acid aptamer is obtained by inserting a base analogue containing a trifluoromethyl structural unit into any position of a natural nucleic acid aptamer or replacing a base. The novel aptamer-nuclide molecular probe is applied to PET / CT (positron emission tomography / computed tomography) molecular imaging as a developing agent. According to the present invention, the novel specific SGC8 aptamer PET imaging probe [89Zr] DFO-SGC8-F of the PTK7 is created, such that the non-invasive visual detection of the PTK7 receptor protein expression is achieved, the non-invasive molecular imaging of the malignant colorectal cancer is further achieved, and the probe has characteristics of high specificity and high stability.

Description

technical field [0001] The invention relates to the fields of biotechnology and molecular imaging, in particular to a novel molecular imaging probe for diagnosing malignant colorectal tumors. Background technique [0002] The imaging examination of tumor tissue is of great significance for the prevention and treatment of cancer. At present, methods such as fluorescence, ultrasound, nuclear magnetic resonance (MRI), computerized tomography (CT), and positron emission tomography (PET-CT) are usually used clinically to track and image tumors. Among them, PET / CT, as an imaging technique for clinical examination of nuclear medicine, is currently the only technique that uses anatomical morphology to perform functional, metabolic and receptor imaging. It is non-invasive and provides three-dimensional and functional images of the whole body. Therefore, PET / CT technology has a large number of applications in the clinical medical imaging of oncology and the study of cancer spread. ...

Claims

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Application Information

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IPC IPC(8): A61K51/04
CPCA61K51/0491A61K51/0482A61K51/0474
Inventor 谭蔚泓丁玎赵海涛刘建军
Owner RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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