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Prostate specific membrane antigen targeting molecular probe as well as preparation method and application thereof

A prostate-specific, molecular-targeting technology, applied in the field of prostate-specific membrane antigen-targeted molecular probes and preparations, can solve problems such as short half-life and less isotopes, and achieve high binding affinity and good biocompatibility

Active Publication Date: 2021-06-15
AFFILIATED HOSPITAL OF JIANGNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

despite the 68 A Ga-labeled targeted PSMA tracer shows good clinical imaging properties for prostate cancer, but it has a shorter half-life and 68 Ga generator flushing fluid has very few isotopes

Method used

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  • Prostate specific membrane antigen targeting molecular probe as well as preparation method and application thereof
  • Prostate specific membrane antigen targeting molecular probe as well as preparation method and application thereof
  • Prostate specific membrane antigen targeting molecular probe as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0070] Example 1 Preparation of Prostate Specific Membrane Antigen Targeting Molecular Probe Precursor

[0071] This embodiment provides a prostate specific membrane antigen targeting molecular probe precursor, which has the structure shown in the following formula:

[0072]

[0073] The preparation method is as follows:

[0074] (1) The synthetic route of compound 4 is as follows:

[0075]

[0076] In a round bottom flask (100 mL), compound 1-4 (di-tert-butyl L-glutamate hydrochloride) (500 mg, 1.7 mmol) was dissolved in dichloromethane (20 mL), triethylamine (0.6 mL ) and -dimethylaminopyridine (8mg) in suspension. N'N-carbonyldiimidazole (300 mg, 1.86 mmol) was added to the reaction mixture and stirred at room temperature overnight. The reaction completed mixture was diluted with dichloromethane (20 mL), and extracted from saturated sodium chloride solution. After the extraction was complete, the organic phase was dried over anhydrous sodium sulfate and concentrat...

Embodiment 2

[0096] Example 2 Prostate-specific membrane antigen targeting molecular probe

[0097] This embodiment provides the prostate-specific membrane antigen targeting molecular probe [ 18 F]GLNTGT, has the structure shown in the following formula:

[0098]

[0099] The synthetic route is as follows:

[0100]

[0101] Obtain 7.4GBq of [ 18 F] Fluoride, bombarded with 18 MeV protons at high voltage [ 18 O] Water targets, and rinsed with pyridazine-HCl Buffer (pH = 2.5, 1 M, 300 μL) was placed directly into a centrifuge tube containing the non-radioactive compound GLNTGT (25 mM, 30 μL). The reaction mixture was incubated at 80°C for 35 minutes. Radioactive HPLC detected [ 18 F] Successful flagging of GLNTGT (results such as Figure 8 middle line B). will mark the [ 18F] GLNTGT reaction mixture was transferred to a 40 mL centrifuge tube with 20 mL deionized water. The RP-C18 chromatographic column was washed twice with the mixture in the centrifuge tube (10mL / time). The ...

experiment example 1

[0104] Experimental Example 1 Serum Stability

[0105] With the tracer prepared in embodiment 2 [ 18 F] GLNTGT (20 μL, 0.074 MBq) was added to separate centrifuge tubes containing fetal bovine serum (90 μL) and sterile phosphate-buffered saline (PBS, pH=7.4) (90 μL), respectively. The centrifuge tubes were then incubated at 37 °C for 1 h, 2 h and 4 h. 10 μL of the incubation samples were collected at each time point, and then 10 μL of acetonitrile were added to each of them to precipitate serum proteins. The supernatant for radio-HPLC analysis was obtained by centrifuging the incubated samples (12000 rpm, 1 min). The radiation-HPLC analysis method of the supernatant is shown in Table 3 in Example 2.

[0106] The result is as Figure 8 As shown (lines D, E, F and G in the figure), during the 4-hour incubation, [ 18 F] GLNTGT is always stable in PBS and fetal bovine serum.

[0107] Experimental Example 2 Lipophilicity

[0108] Determination of the tracer by the shake flas...

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Abstract

The invention relates to the field of medicine, in particular to a prostate specific membrane antigen targeting molecular probe and a preparation method and application thereof. The prostate specific membrane antigen targeting molecular probe [18F] GLNTGT provided by the invention has good stability in vitro and shows good biocompatibility in prostate cancer cells with different PSMA expressions, and specific targeting on PSMA determines that the tracer [18F] GLNTGT has high tumor cell uptake rate and high binding affinity on PSMA. Compared with a control tracer agent [18F] AlF-NOTA-RGD2, a mouse of the [18F] GLNTGT group has a higher target-to-cost ratio. Although the tracer [18F] GLNTGT has some limitations in cell and in-vivo CT signal detection experiments, a reference is still provided for the development of PET / CT tracers.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a prostate-specific membrane antigen targeting molecular probe, a preparation method and an application thereof. Background technique [0002] Prostate cancer is a common malignancy in adult males worldwide and is the fifth leading cause of cancer death in adult males worldwide. Early diagnosis of prostate cancer is critical because the treatment of prostate cancer depends largely on the stage of the disease. Currently, there are many clinical methods for diagnosing prostate cancer, including needle biopsy, magnetic resonance imaging (MRI), computed tomography (CT), single photon and positron emission tomography (SPECT / PET), etc. In the clinical diagnosis of all malignant tumors, CT imaging is widely used due to its high spatial resolution and anatomical imaging capabilities. However, it has limited soft tissue resolution. PET tracers are used for imaging of multiple tumor biomarkers, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F5/02C09K11/06A61P35/00A61K51/04A61K49/04A61K101/02
CPCC07F5/02C09K11/06A61K51/0453A61K49/04A61P35/00C09K2211/1011C09K2211/1007
Inventor 郁春景张雨郭一睿陈礼平茆勇
Owner AFFILIATED HOSPITAL OF JIANGNAN UNIV
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