Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry and Czech Advanced Technology and Research Institute, Palacky University, Olomouc 779 00, Czech Republic.
Department of Microbiology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, Olomouc 775 15, Czech Republic.
J Med Chem. 2023 Jun 8;66(11):7584-7593. doi: 10.1021/acs.jmedchem.3c00469. Epub 2023 May 30.
Bacteria from the complex are generally considered to be non-pathogenic to the healthy population. However, some of these species may cause serious nosocomial infections in immunocompromised patients; as such, it is essential to diagnose these infections rapidly so that adequate treatment can be initiated. We report here the use of a radiolabeled siderophore, ornibactin (ORNB), for positron emission tomography imaging. We successfully radiolabeled ORNB with gallium-68 with high radiochemical purity and proved that the resulting complex has optimal characteristics. In mice, the complex did not show excessive accumulation in organs and was excreted in the urine. We demonstrated that the [Ga]Ga-ORNB complex accumulates at the site of infection, including pneumonia, in two animal infection models. These results suggest that [Ga]Ga-ORNB is a promising tool for the diagnosis, monitoring, and evaluation of the therapeutic response to complex infection.
通常认为复合体中的细菌对健康人群没有致病性。然而，这些物种中的一些可能会导致免疫功能低下的患者发生严重的医院获得性感染；因此，快速诊断这些感染至关重要，以便能够及时开始进行适当的治疗。我们在此报告了使用放射性标记的铁载体奥尼巴辛（ORNB）进行正电子发射断层扫描成像。我们成功地用镓-68 对 ORNB 进行了放射性标记，具有很高的放射化学纯度，并证明所得配合物具有最佳的特性。在小鼠中，该配合物在器官中没有过度积累，而是通过尿液排出。我们证明，该[Ga]Ga-ORNB 配合物在两种动物感染模型中积聚在感染部位，包括肺炎。这些结果表明，[Ga]Ga-ORNB 是一种很有前途的工具，可用于诊断、监测和评估对复合体感染的治疗反应。
