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 <i>in vivo</i> 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 <b>1</b>, by conjugating neomycin, an aminoglycoside antibiotic, with Dotarem (Gd-DOTA, an FDA approved T₁-weighted MRI contrast agent). The T₁ relaxivity of probe <b>1</b> was found to be comparable to that of Gd-DOTA; additionally, probe <b>1</b>-treated bacteria generated a significantly brighter T₁-weighted MR signal than Gd-DOTA-treated bacteria. More importantly, <i>in vitro</i> cellular studies and preliminary <i>in vivo</i> MRI demonstrated probe <b>1</b> exhibits the ability to efficiently target bacteria over macrophage-like cells, indicating its great potential for high-resolution imaging of bacterial infections <i>in vivo</i>

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 <i>in vivo</i> 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 <b>1</b>, by conjugating neomycin, an aminoglycoside antibiotic, with Dotarem (Gd-DOTA, an FDA approved T₁-weighted MRI contrast agent). The T₁ relaxivity of probe <b>1</b> was found to be comparable to that of Gd-DOTA; additionally, probe <b>1</b>-treated bacteria generated a significantly brighter T₁-weighted MR signal than Gd-DOTA-treated bacteria. More importantly, <i>in vitro</i> cellular studies and preliminary <i>in vivo</i> MRI demonstrated probe <b>1</b> exhibits the ability to efficiently target bacteria over macrophage-like cells, indicating its great potential for high-resolution imaging of bacterial infections <i>in vivo</i>

HI antibody dynamics in infected patients and vaccinated people.

<p>Note: Detection limitation (HI titer <20) is indicated by the dotted line. Error bar indicates ± standard deviation (SD) from different individual study subjects. * indicates significant differences (<i>P</i><0.01) between results of day 30 and day 180.</p

Positive rate and GMT of 2009 H1N1 virus antibody in a follow-up study of natural infection patients and vaccinated people, Guangzhou, 2009.

<p>*p<0.05,</p><p>**p<0.01.</p

Positive antibody and GMT in different age group of vaccinated people.

<p>Positive antibody and GMT in different age group of vaccinated people.</p

analysis of potential risk factors associated with the death of pH1N1 influenza severe cases in the first epidemic year.^*

<p>*Four pH1N1 sever cases were reported in the second epidemic year with one death and the dead case also had pre-existing chronic pulmonary disease.</p>#<p>OR = odds ratio.</p

The frequency, scale and duration of outbreaks of influenza in the first and second epidemic year.

<p>*Average number of outbreaks/month.</p>&<p>Average attck rate/outbreak (%).</p>#<p>Average days/outbreak±SD.</p

Seasonal distribution of influenza in Guangzhou from May 2008 to April 2011.

<p>(A) Confirmed cases of seasonal influenza (Seasonal, including H1N1, H3N2 and B) and pH1N1 influenza are shown in the indicated time. (B) Confirmed cases of seasonal influenza caused by subtypes H1N1, H3N2 and B are shown in the indicated time.</p

Severe disease and fatality rates of pH1N1 and seasonal influenza in Guangzhou.

<p>(A) Severe disease rate (% of patients progressed to severe disease) of pH1N1 influenza in the first (1st pH1N1) and second (2nd pH1N1) epidemic year and of seasonal influenza in the second epidemic year (2nd seasonal). (B) Fatality rate (deaths/10000) of pH1N1 influenza in the first (1st pH1N1) and second (2nd pH1N1) epidemic year and of seasonal influenza in the second year (2nd seasonal).</p

Additional file 1: Table S1. of Overexpression of lncRNA IGFBP4–1 reprograms energy metabolism to promote lung cancer progression

Sequence of primers using for qRT-PCR analysis (DOCX 12 kb