School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences , Jinan, Shandong 250200, China.
Institute of Materia Medica, Shandong Academy of Medical Sciences, Key Laboratory for Biotech-Drugs Ministry of Health, Key Laboratory for Rare & Uncommon Diseases of Shandong Province , Jinan, Shandong 250062, China.
Anal Chem. 2018 Feb 6;90(3):1934-1940. doi: 10.1021/acs.analchem.7b04029. Epub 2018 Jan 17.
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 T-weighted MRI contrast agent). The T relaxivity of probe 1 was found to be comparable to that of Gd-DOTA; additionally, probe 1-treated bacteria generated a significantly brighter T-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.
磁共振成像（MRI）是一种强大的诊断技术，它可以深入组织，提供出色的空间分辨率，而无需电离辐射或有害放射性核素。然而，临床上用 MRI 诊断细菌感染受到缺乏高弛豫率、靶向能力以及细菌穿透性和特异性的对比剂的严重阻碍。在这里，我们报告了首例基于钆（Gd）的细菌特异性靶向 MRI 对比剂探针 1 的开发，该探针通过将新霉素（一种氨基糖苷类抗生素）与 Dotarem（Gd-DOTA，一种 FDA 批准的 T 加权 MRI 对比剂）偶联而成。探针 1 的 T1 弛豫率与 Gd-DOTA 相当；此外，探针 1 处理的细菌产生的 T1 加权 MR 信号比 Gd-DOTA 处理的细菌亮得多。更重要的是，体外细胞研究和初步体内 MRI 表明，探针 1 能够有效地靶向细菌而不是巨噬细胞样细胞，这表明其在体内高分辨率成像细菌感染方面具有巨大的潜力。
