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Two-dimensional palladium-based probe with radioiodine labeling and preparation method and application of probe

A radioactive iodine and palladium-based technology, applied in the field of medical imaging probes, can solve the problems of insufficient combination of drugs and targets, unsatisfactory target/non-target ratios, and increased doses. Function information, effect of increasing distance

Active Publication Date: 2019-07-16
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Unfortunately, when applied to atherosclerotic plaque imaging, there are often problems such as fast clearance and unsatisfactory target / non-target ratio
Those of ordinary skill in the art know that if the drug circulates in the blood vessels for too short a time or is quickly cleared by the body, the combination of the drug and the target will be insufficient.
In this case, the prior art has to increase the dosage to make the drug effect more obvious

Method used

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  • Two-dimensional palladium-based probe with radioiodine labeling and preparation method and application of probe
  • Two-dimensional palladium-based probe with radioiodine labeling and preparation method and application of probe
  • Two-dimensional palladium-based probe with radioiodine labeling and preparation method and application of probe

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] The synthetic route of the present embodiment is as follows:

[0045]

[0046] Specifically include the following steps:

[0047] 1) Synthesis of FA-PEG-SH

[0048] I) Synthesis of FA-NHS: After dissolving 1-2g folic acid in dimethyl sulfoxide, add 1-1.5 equivalents of N-hydroxysuccinimide (NHS) and 1-1.5 equivalents of dicyclohexylcarbodiethylene Amine (DCC), activated overnight in the dark and filtered.

[0049] II) Synthesis of FA-PEG-SH: the equivalent amount of NH 2 -PEG-SH (molecular weight 3400Da) was dissolved in DMSO and added dropwise to the above FA-NHS filtrate, adding 0.5-1 equivalent of N,N-diisopropylethylamine (DIPEA), and reacted at 20-50°C 1-2 days. After the reaction is complete, transfer the reaction solution to a dialysis belt with a molecular weight cut-off of 1000, first dialyze with PBS7.4 buffer solution for 1-2 days, and then dialyze with pure water for 1-2 days. After the dialysis, the liquid in the dialysis zone was collected and free...

Embodiment 2

[0061] 1) 131 In vitro stability determination of I-Pd@Au-PEG-FA

[0062] The above-mentioned embodiment 1 is made 131 I-Pd@Au-PEG-FA probe was incubated with normal saline, PBS 7.4 buffer and mouse serum for 24 hours. Stability was determined by TLC (polyamide film / physiological saline system) method. Such as Figure 4 Shown: the present invention 131 The I-Pd@Au-PEG-FA probe can exist stably in the above systems, and its radiochemical purity does not change significantly.

[0063] 2) 125 I-Pd@Au-PEG-FA in ApoE - / - SPECT imaging and vascular autoradiography in model mice

[0064] ApoE - / - Gene knockout mice were fed a special high-fat diet for 2-6 months to form plaques. Before injecting the radiolabeled probe, inject 0.1mL NaI solution (2mg) in advance to seal the mouse thyroid. Prepared according to the example 125 I-Pd@Au-PEG-FA dispersion, take 0.1mL (about 37MBq) and inject it into ApoE - / - Tail veins of knockout mice (about 20 g body weight) were subjected t...

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Abstract

The invention discloses a two-dimensional palladium-based probe with radioiodine labeling and a preparation method and application of the probe. The probe comprises a two-dimensional palladium-based nanomaterial, a PEG linking molecule, a targeting group R and radioiodine, a thiol group is arranged at one end of the PEG linking molecule, a modifiable group is arranged at the other end of the PEG linking molecule, one end of the PEG linking molecule is linked to the two-dimensional palladium-based nanomaterial through the above thiol group, the other end is linked to the targeting group R through the modifiable group, and radioiodine is directly labelled on the two-dimensional palladium-based nanomaterial. According to the present invention, a plurality of radioiodine can be carried on a unit of nanocarrier based on the strong binding force between the two-dimensional palladium-based nanomaterial and halogen ions, the probe has the characteristics of strong labeling ability, short labeling time, high labeling yield and no need of subsequent purification before application, and is more conducive to commercial application and clinical promotion of markers.

Description

technical field [0001] The invention belongs to the technical field of medical imaging probes, and in particular relates to a radioactive iodine-labeled two-dimensional palladium-based probe and its preparation method and application. Background technique [0002] According to the "China Cardiovascular Disease Report 2017", my country's cardiovascular disease prevention and treatment is facing severe challenges. Cardiovascular disease deaths accounted for more than 40% of the residents' disease deaths, ranking first, higher than tumors and other diseases. According to the data of the World Health Organization, the mortality rate of cardiovascular disease in my country is significantly higher than that of Japan and developed countries in Europe and America. Atherosclerosis is the most important cause of cardiovascular diseases. How to detect plaque lesions early, so as to take effective treatment and reduce the mortality of cardiovascular diseases is a major issue for medica...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K51/04A61K51/06A61K51/08A61K101/02
CPCA61K51/0459A61K51/0491A61K51/06A61K51/082A61K51/083A61P9/10
Inventor 郭志德张现忠郑南峰陈美文雪君李靖超
Owner XIAMEN UNIV
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