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A kind of fluorescent molecular probe targeting psma and its preparation method and application

A fluorescent molecular probe and targeting technology, which is applied in the field of PSMA-targeted fluorescent molecular probe and its preparation, can solve the problems of poor tumor tissue permeability, short residence time, slow clearance, etc., and achieve long tumor enrichment time, Enhanced binding ability, excellent TBR effect

Active Publication Date: 2022-07-15
GUANGDONG INFOCUS VISION BIOMEDICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] 1) Small molecule fluorescent probes have a short half-life, fast metabolism, and short residence time in tumors, making it difficult to achieve ideal TBR;
[0009] 2) Antibody-based fluorescent probes have a long half-life and slow clearance, and the large molecular weight of the antibody leads to poor tumor tissue permeability. After injection, delayed imaging (delayed for 2-4 days) is required to achieve the ideal TBR, resulting in increased nursing costs and difficulty
In addition, monoclonal antibodies are potentially immunogenic and prone to safety issues;
[0010] 3) It cannot well meet the requirements of intraoperative tumor-specific imaging, and there is a large room for improvement in sensitivity and specificity

Method used

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  • A kind of fluorescent molecular probe targeting psma and its preparation method and application
  • A kind of fluorescent molecular probe targeting psma and its preparation method and application
  • A kind of fluorescent molecular probe targeting psma and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0114] Example 1 Synthesis method of fluorescent molecular probe (compound 6)

[0115]

[0116] Resin activation: Compound 1 (Fmoc-Lys(Dde)-Wang resin, purchased from Nanjing Peptide Industry Biotechnology Co., Ltd., R61124, 0.3-0.8mmol / g, 100-200mesh, 1g) was first mixed with hexahydropyridine / DMF Solvent I (25%:75% by volume) removed the N-terminal Fmoc protecting group to make the N-terminal free amino group.

[0117] Accessing amino acids: N,N disuccinimidyl carbonate (3.2 mmol) and DIPEA (10 mmol) and H-Glu(OtBu)-OtBu (3.2 mmol) were dissolved in 20 ml of DMF and added to the above-mentioned 12-hour Resin (de-Fmoc protected compound 1), reacted for 24 hours to obtain compound 2.

[0118] Compounds 3, 4, and 5 use a similar grafting operation as above:

[0119] Compound 3: After removing the Dde protecting group of the side chain of Lys on the resin (ie compound 2) with 2% hydrazine hydrate / DMF solution (hydrazine hydrate: DMF=2%: 98%), add 3 times equivalent of Fmoc-...

Embodiment 2

[0125] Example 2 Synthesis method of fluorescent molecular probes (compounds 11 and 12)

[0126]

[0127] Compound 7: use 25% hexahydropyridine / DMF (volume ratio, the same meaning as above) to remove the Fmoc protecting group in compound 3 to make the N-terminus of 2-Nal a free amino group, add 3 times the equivalent of N-Fmoc-trans-4-carbamate cyclohexanecarboxylic acid / HOBt / DIC (that is, the consumption of N-Fmoc-trans-4-aminomethylcyclohexanecarboxylic acid, HOBt, and DIC are all 3 times the molar weight of the resin) and react for 24 hours at room temperature, A grafting reaction was performed to introduce trans-4-aminomethylcyclohexanecarboxylic acid.

[0128]

[0129] Compound 8: remove the Fmoc protecting group on compound 7 with 25% hexahydropyridine / DMF (volume ratio), add 3 times the equivalent of N-Fmoc-N'-[1-(4,4-dimethyl-2,6- Dioxocyclohexylidene)ethyl]-lysine / HOBt / DIC (ie, refers to N-Fmoc-N'-[1-(4,4-dimethyl-2,6-dioxocyclohexyl) The amount of subunit) et...

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Abstract

The invention relates to the technical field of disease detection, in particular to a fluorescent molecular probe targeting PSMA and a preparation method and application thereof. In the fluorescent molecular probe, the target head is a PSMA small molecule inhibitor or an oligopeptide substrate; the load is a fluorescent group; with or without an albumin binding group. The fluorescent molecular probe of the invention enhances the binding ability of the probe to PSMA, and increases the internalization mediated by PSMA; the half-life is long, the tumor enrichment time is long, and the accumulation of the targeted probe in prostate tumor tissue is increased; tumor fluorescence The signal is significant and stable for a long time; the fluorescent molecular probe of the present invention exhibits excellent TBR both in vivo and in vitro imaging.

Description

technical field [0001] The invention belongs to the technical field of fluorescent molecular probes, and particularly relates to a fluorescent molecular probe targeting PSMA and a preparation method and application thereof. Background technique [0002] Prostate cancer (PCa) is the most common malignancy in men and the third leading cause of cancer-related death in men worldwide. According to statistics, currently about 1-2% of men die from prostate cancer. As human beings enter an aging society, this disease that threatens the health of men around the world will become increasingly serious. Although the early diagnosis and treatment technology of prostate cancer has developed rapidly in recent years, there are still many patients with re-elevation of serum prostate specific antigen (PSA) or imaging progress after initial treatment. Treatment options for prostate cancer include surgery, radiation therapy, and endocrine therapy. Patients diagnosed with early-stage localize...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/00
CPCA61K49/0093A61K49/0021
Inventor 侯征李九鹏张茜杨大伟
Owner GUANGDONG INFOCUS VISION BIOMEDICAL TECH CO LTD
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