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Dual-targeting multi-modal molecular imaging probe and preparation method and application thereof

A molecular imaging, multimodal technology, applied in general/multifunctional contrast agents, pharmaceutical formulations, echo/ultrasound imaging agents, etc., can solve problems such as unsatisfactory treatment effects

Active Publication Date: 2019-10-22
XIANGYA HOSPITAL CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] With the deepening of basic research and the development of high-throughput sequencing technology, a series of important breakthroughs have been made in the study of the mechanism of tumorigenesis and malignant progression of glioma, and many key factors related to glioma have also been identified. Molecular markers (biomarkers), and corresponding biological agents have been developed for these targets, but their therapeutic effects are not ideal

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  • Dual-targeting multi-modal molecular imaging probe and preparation method and application thereof
  • Dual-targeting multi-modal molecular imaging probe and preparation method and application thereof
  • Dual-targeting multi-modal molecular imaging probe and preparation method and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Embodiment 1: Probe preparation process

[0058] 1. Synthesis of hydrophobic SPIO nano-cores: Take 0.7g of iron acetylacetonate, 4.45g of oleic acid, and 4.07g of oleylamine in a 100ml double-necked flask, shake and mix well, fix it on a constant temperature magnetic stirrer, and connect it to a catheter to feed argon Air for 5 minutes to expel the air in the system. Turn on the power to heat the system, raise the temperature of the system to 120°C within half an hour, keep the temperature at 120°C for 2 hours; then, gradually raise the temperature to 220°C within half an hour, and control the system at 220°C for 30 minutes ; Finally, after adjusting the temperature to 300°C within 1 hour, the reaction was continued for 30 minutes under these conditions. After natural cooling, four cycles of ethanol and hexane were used to precipitate and resuspend, and finally the precipitate was collected by centrifugation, dissolved in toluene, and the iron content was adjusted to 1...

Embodiment 2

[0067] Example 2: Detection of EGFR and SEC61G in GBM by dual targeting probes

[0068] 1. From figure 2The results can be seen: EGFR and SEC61G have a trend of "symbiosis" no matter at the level of genome copy number or mRNA expression pattern; in the research cohort we selected, 33% of GBM patients have Amplification of the copy number of the SEC61G gene; Interestingly, these GBM patients with SEC61G amplification events also have amplification of the EGFR gene; moreover, this amplification event can have a direct impact on the transcription of its mRNA: Cases with amplification events also had significantly increased levels of corresponding mRNA ( figure 2 A); At the same time, the changes in the copy numbers of EGFR and SEC61G on the genome level tend to be synchronized ( figure 2 B); And on the water of mRNA, the Spearman's correlation coefficient of the expression level of two proteins is 0.58, and Pearson's correlation coefficient is 0.65, and P value is all less t...

Embodiment 3

[0085] Example 3: In vivo fluorescence, NMR and photoacoustic imaging effect experiments of dual-target imaging probes

[0086] 1. Establishment of animal models

[0087] Construction of a subcutaneous tumor model: cells in the exponential growth phase and with strong cell viability were selected for digestion, centrifugation, and collection. After washing with PBS for 3 times, they were evenly mixed with PBS:Matrigel at a volume ratio of 1:1, and adjusted Cell concentration up to 10 7 Units / ml; Use an insulin needle to draw 100ul of the mixed cell suspension on the back of nude mice for subcutaneous injection. When the needle tip feels a breakthrough, advance the needle 2-3mm in parallel. Be careful not to puncture the skin. Inject slowly, and the skin will bulge and turn white It means that the injection is successful, put the mouse back and continue to raise it, observe it regularly, and start the experiment when its diameter is about 0.5mm.

[0088] Construction of the o...

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Abstract

The invention discloses a dual-targeting multi-modal molecular imaging probe and a preparation method and application thereof. The probe of the invention is a tri-modal dual-targeting probe with nuclear magnetic, photoacoustic and near-infrared fluorescence signals. By adopting a unique EGFR and SEC61G dual-targeting strategy, the probe can significantly improve the accuracy of preoperative tumordiagnosis and potential intraoperative navigation application, and has broad application prospects and transformation value.

Description

technical field [0001] The invention belongs to the technical field of molecular image probes, and relates to a dual-target multimodal molecular image probe and its preparation method and application. Background technique [0002] Glioma is the most common malignant primary brain tumor of the central nervous system. According to the statistical report of the diagnosis cases of primary brain tumors and other central nervous system tumors collected from 2010 to 2014 released by the American Center for Brain Tumor Registry (CBTRUS), nearly half (47.1%) of the brain tumor cases were glue Glioma patients; and among the patients diagnosed with glioma, nearly 60% (56.1%) were diagnosed as the most malignant glioblastoma (GBM). Due to the nature of glioma tumor cells infiltrating and growing along the white matter fiber bundles, they can invade the adjacent normal brain tissue, so it is very difficult to identify tiny tumor residues during the operation, and the tumor cells cannot ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/00A61K49/14A61K49/16A61K49/22
CPCA61K49/0002A61K49/0034A61K49/0056A61K49/0058A61K49/14A61K49/16A61K49/221
Inventor 黄琦李学军
Owner XIANGYA HOSPITAL CENT SOUTH UNIV
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