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Dual-modal MRI contrast agent with aggregation-induced emission characteristic for liver specific imaging with long circulation lifetime.

Chen Y †‡,  Li M §, Hong Y ‡, Lam JY ‡,  Zheng Q *§, and Tang BZ*†‡∥.

ACS Appl Mater Interfaces. 2014;6(13):10783-91.

†HKUST Shenzhen Research Institute, No. 9 Yuexing 1st RD, South Area, Hi-tech Park Nanshan, Shenzhen 518057, China.
‡Department of Chemistry, Institute for Advanced Study, Division of Biomedical Engineering, Division of Life Science, Institute of Molecular Functional Materials and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science & Technology (HKUST), Clear Water Bay, Kowloon, Hong Kong, China.
§Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
∥Guangdong Innovative Research Team, SCUT-HKUST Joint Research Laboratory, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology (SCUT), Guangzhou 510640, China.
Abstract

We herein report a novel dual-modal MRI contrast agent, TPE-2Gd, for both magnetic and fluorescence imaging. TPE-2Gd consists of a hydrophobic tetraphenylethene (TPE) fluorophore and two hydrophilic gadolinium (Gd) diethylenetriaminepentaacetic acid moieties. As an amphiphilic molecule, TPE-2Gd aggregates into micelles at a high concentration in aqueous medium. These aggregates are highly emissive, showing an aggregation-induced  emission  (AIE) characteristic. TPE-2Gd is used as a fluorescent agent for cell imaging, which demonstrates negligible cytotoxicity and excellent photostability owing to its AIE property. As a magnetic resonance imaging  (MRI) contrast agent, TPE-2Gd exhibits similar longitudinal relaxivity in water (R1,TPE-2Gd = 3.36 ± 0.10 s(-1) per mM of Gd(3+)) as those commercial agents (e.g., Magnevist, R1,magnevist = 3.70 ± 0.02 s(-1) per mM of Gd(3+)). Compared with Magnevist, the circulation lifetime of TPE-2Gd nanoaggregates in living rats is extended from 10 min to 1 h. With relatively high specificity to the liver, the MR imaging could remain hyperintense in liver even after 150 min post injection. These TPE-2Gd nanoparticles can be excreted gradually via renal filtration due to the disassembly of the nanoparticles into small molecules during circulation. TPE-2Gd could thus potentially be used as a liver specific MRI contrast agent for clinical diagnosis.

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Significance statement

Multimodality imaging agents have a promising potential in medical diagnostics, especially dual fluorescence and magnetic resonance imaging (MRI). A new dual MRI-fluorescence contrast agent, TPE-2Gd, was designed and synthesized for liver specific imaging with long circulation lifetime. TPE-2Gd aggregates into micelles at high concentration in aqueous medium due to hydrophobic tetraphenylethene (TPE) fluorophore and two hydrophilic gadolinium (Gd) diethylenetriaminepentaacetic acids moieties. This agent has classic aggregation-induced emission characteristic, which emits strong fluorescence when they aggregate. They can label live cell in vitro and enhance the signal intensity of organs in vivo with long blood circulation lifetime. Especially, the signal intensity in liver still kept at a high level after long time of injection. TPE-2Gd could thus potentially be used as a liver specific MRI contrast agent for clinical diagnosis.

 

Figure Legends

The illustration of nanoaggregates formation and the mechanism of TPE-2Gd. The agents self-aggregate into nanostructure owing to the hydrophobic tetraphenylethene fluorophore and two hydrophilic gadolinium diethylenetriaminepentaacetic acids moieties and work through shortening the T1 relaxation time of protons located around the nanoaggregates. (B) Coronal T1-weighted MR images of rat after intravenous injection of TPE-2Gd with long circulation lifetime.

 

 

Dual-Modal MRI Contrast Agent with Aggregation-Induced Emission Characteristic for Liver Specific Imaging with Long Circulation Lifetime. Global Medical Discovery