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Gadolinium-Labeled Aminoglycoside and Its Potential Application as a Bacteria-Targeting Magnetic Resonance Imaging
Leilei Zhang, Yun Liu1,2, Qingyang Zhang
1School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences , Jinan, Shandong 250200, China.
Abstract:
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.
Insights
Researchers developed a novel gadolinium-based MRI contrast agent, probe 1, by linking neomycin to Dotarem. This new agent specifically targets bacteria, enhancing MRI visualization of bacterial infections in vivo.
Area of Science:
- Biomedical Imaging
- Medical Chemistry
- Infectious Disease Diagnostics
Background:
- Magnetic resonance imaging (MRI) offers deep tissue penetration and high spatial resolution without ionizing radiation.
- Diagnosing bacterial infections via MRI is challenging due to a lack of targeted, high-relaxivity contrast agents.
- Existing MRI contrast agents lack specificity for bacterial targets.
Purpose of the Study:
- To develop the first gadolinium-based MRI contrast agent with bacteria-specific targeting capabilities.
- To enhance the in vivo imaging of bacterial infections using MRI.
- To overcome the limitations of current MRI contrast agents in infection detection.
Main Methods:
- Conjugation of neomycin (an aminoglycoside antibiotic) with Dotarem (Gd-DOTA), an FDA-approved MRI contrast agent, to create probe 1.
- Assessment of probe 1's T1 relaxivity compared to Gd-DOTA.
- In vitro cellular studies and preliminary in vivo MRI to evaluate targeting specificity and efficacy against bacteria and macrophage-like cells.
Main Results:
- Probe 1 demonstrated T1 relaxivity comparable to Gd-DOTA.
- Bacteria treated with probe 1 showed a significantly brighter T1-weighted MR signal than those treated with Gd-DOTA.
- In vitro and in vivo studies confirmed probe 1's efficient targeting of bacteria over macrophage-like cells.
Conclusions:
- Probe 1 represents the first gadolinium-based MRI contrast agent specifically designed for bacterial targeting.
- The developed agent shows significant potential for high-resolution in vivo imaging of bacterial infections.
- This advancement could improve the diagnosis and management of bacterial infections using MRI.
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