Gadolinium-Labeled Aminoglycoside and Its Potential Application as a Bacteria-Targeting Magnetic Resonance Imaging Contrast Agent

Magnetic resonance imaging (MRI) is a powerful diagnostic technique that can penetrate deep into tissue providing excellent spatial resolution without the need for ionizing radiation or harmful radionuclides. However, diagnosing bacterial infections in vivo with clinical MRI is severely hampered by...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2018-02, Vol.90 (3), p.1934-1940
Main Authors: Zhang, Leilei, Liu, Yun, Zhang, Qingyang, Li, Tiegang, Yang, Min, Yao, Qingqiang, Xie, Xilei, Hu, Hai-Yu
Format: Article
Language:English
Subjects:
Aminoglycoside antibiotics
Antibiotics
Bacteria
Chemical elements
Chemistry
Contrast agents
Diagnostic systems
Gadolinium
Image resolution
In vivo methods and tests
Infections
Ionizing radiation
Macrophages
Magnetic resonance imaging
Neomycin
NMR
Nuclear magnetic resonance
Radioisotopes
Resonance
Spatial discrimination
Spatial resolution
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Summary:Magnetic resonance imaging (MRI) is a powerful diagnostic technique that can penetrate deep into tissue providing excellent spatial resolution without the need for ionizing radiation or harmful radionuclides. However, diagnosing bacterial infections in vivo with clinical MRI is severely hampered by the lack of contrast agents with high relaxivity, targeting capabilities, and bacterial penetration and specificity. Here, we report the development of the first gadolinium (Gd)-based bacteria-specific targeting MRI contrast agent, probe 1, by conjugating neomycin, an aminoglycoside antibiotic, with Dotarem (Gd-DOTA, an FDA approved T1-weighted MRI contrast agent). The T1 relaxivity of probe 1 was found to be comparable to that of Gd-DOTA; additionally, probe 1-treated bacteria generated a significantly brighter T1-weighted MR signal than Gd-DOTA-treated bacteria. More importantly, in vitro cellular studies and preliminary in vivo MRI demonstrated probe 1 exhibits the ability to efficiently target bacteria over macrophage-like cells, indicating its great potential for high-resolution imaging of bacterial infections in vivo.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.7b04029