<18>F-labeled aggregation-induced emission (AIE) fluorescent/positron emission tomography (PET) dual-mode probe, and preparation method and application thereof

Abstract

The invention discloses an <18>F-labeled aggregation-induced emission (AIE) fluorescent / positron emission tomography (PET) dual-mode probe, and a preparation method and application thereof. The compound is denoted as <18>F-TPE-TEG, and has a following structure. The synthesis method of a labelled precursor of the compound comprises the following steps: firstly, adding 2-bromo-1,1,2-triphenylethylene, 4-hydroxyphenylboronic acid and tetrabutylammonium bromide into tetrahydrofuran, and taking K2CO3 and tetrakis(triphenylphosphine)palladium as catalysts to carry out a reaction to obtain 4-hydroxytetraphenylethylene; then dissolving triethylene glycol, triethylamine and p-toluenesulfonyl chloride in dichloromethane, and carrying out a reaction to obtain 8-p-toluenesulfonyloxy-3,6-dioxyoctanol;adding the 4-hydroxytetraphenylethylene, K2CO3, the 8-p-toluenesulfonyloxy-3,6-dioxyoctanol into acetonitrile, and carrying out a reaction to obtain 8-tetraphenylethyleneoxy-3,6-dioxyoctanol; and finally, dissolving the 8-tetraphenylethyleneoxy-3,6-dioxyoctanol, p-toluenesulfonyl chloride and triethylamine in dichloromethane, and carrying out a reaction to obtain the labelled precursor. The <18>F-labeled compound can be used as an AIE fluorescent / PET dual-mode probe to be applied to tumor imaging research.

Description

technical field [0001] The invention belongs to the technical field of radiopharmaceuticals and nuclear medicine, and specifically relates to a 18 F-labeled AIE fluorescence / PET dual-mode probe compound and its preparation method and application. Background technique [0002] Positron Emission Tomography (PET) is currently the only new imaging technique that can display biomolecular metabolism, receptors, and neurotransmitter activities in vivo. It has been widely used in the diagnosis and differential diagnosis of various diseases, Efficacy evaluation, organ function research and new drug development, etc. PET imaging technology has high sensitivity, high specificity, and strong penetrability, and it can be used for whole-body imaging, and images of various regions of the whole body can be obtained in one-time whole-body imaging examination. PET is an imaging that reflects molecular metabolism. When the disease is in the stage of molecular level changes in the early stage...

AI Technical Summary

Problems solved by technology

However, PET imaging also has its inherent shortcomings, which has low spatial resolution and cannot accurately locate the lesion.

[0004] Most of the existing fluorescent / PET dual-mode probes are traditional fluorescent molecules labeled with metal nuclides, such as 68 Ga has a shorter half-life, while 64 Cu has a longer half-life and is not suitable for clinical diagnostic research, so it is difficult to be promoted in clinical applications.

In addition, traditional fluorescent molecules are prone to aggregate fluorescence quenching (ACQ) after aggregation at higher concentrations, resulting in fluorescence disappearance.

Therefore, its use concentration needs to be controlled in a very low concentration range, which in turn will cause it to be prone to photobleaching, resulting in a significant decrease in fluorescence quantum efficiency, and the imaging time is greatly limited

18 The imaging studies of F-labeled traditional fluorescent molecules have also been reported, but limited by the shortcomings of traditional fluorescent molecules, the imaging effect still needs to be improved

[0005] Currently, no use 18 Research reports on F nuclide-labeled AIE molecules, the invention discloses a 18 F-labeled AIE fluorescence / PET dual-mode probe and its synthesis method and application

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