Misslinger Matthias, Petrik Milos, Pfister Joachim, Hubmann Isabella, Bendova Katerina, Decristoforo Clemens, Haas Hubertus
Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria.
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 77900 Olomouc, Czech Republic.
J Fungi (Basel). 2021 Sep 8;7(9):734. doi: 10.3390/jof7090734.
Fungal infections are a serious threat, especially for immunocompromised patients. Early and reliable diagnosis is crucial to treat such infections. The bacterially produced siderophore desferrioxamine B (DFO-B) is utilized by a variety of microorganisms for iron acquisition, while mammalian cells lack the uptake of DFO-B chelates. DFO-B is clinically approved for a variety of long-term chelation therapies. Recently, DFO-B-complexed gallium-68 ([Ga]Ga-DFO-B) was shown to enable molecular imaging of bacterial infections by positron emission tomography (PET). Here, we demonstrate that [Ga]Ga-DFO-B can also be used for the preclinical molecular imaging of pulmonary infection caused by the fungal pathogen in a rat aspergillosis model. Moreover, by combining in vitro uptake studies and the chemical modification of DFO-B, we show that the cellular transport efficacy of ferrioxamine-type siderophores is impacted by the charge of the molecule and, consequently, the environmental pH. The chemical derivatization has potential implications for its diagnostic use and characterizes transport features of ferrioxamine-type siderophores.
真菌感染是一个严重威胁，尤其是对免疫功能低下的患者。早期且可靠的诊断对于治疗此类感染至关重要。细菌产生的铁载体去铁胺B（DFO-B）被多种微生物用于获取铁，而哺乳动物细胞缺乏对DFO-B螯合物的摄取。DFO-B在临床上被批准用于多种长期螯合疗法。最近，DFO-B复合的镓-68（[Ga]Ga-DFO-B）已被证明能够通过正电子发射断层扫描（PET）对细菌感染进行分子成像。在此，我们证明[Ga]Ga-DFO-B也可用于大鼠曲霉病模型中由真菌病原体引起的肺部感染的临床前分子成像。此外，通过结合体外摄取研究和DFO-B的化学修饰，我们表明铁胺型铁载体的细胞转运效率受分子电荷以及环境pH的影响。化学衍生化对其诊断用途具有潜在影响，并表征了铁胺型铁载体的转运特征。
