n-n--n---triacetylfusarinine-c and Mycoses

Siderophores play an important role in fungal virulence, serving as trackers for

Topics: Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Fluoresceins; Humans; Iron; Isothiocyanates; Membrane Transport Proteins; Mice; Mycoses; Siderophores; Virulence

Aspergillus fumigatus produces the siderophore triacetylfusarinine C (TAFC) for iron acquisition which is essential for its virulence. Therefore, TAFC is a specific marker for invasive aspergillosis. We have shown previously that positron emission tomography (PET) imaging with [. Fifteen TAFC derivatives were prepared and labeled with gallium-68. In vitro uptake assays were carried out in A. fumigatus under iron-replete as well as iron-depleted conditions and distribution coefficient was determined. Based on these assays, three compounds, [. In vitro uptake studies using A. fumigatus revealed specific uptake of mono- and trisubstituted TAFC derivatives at RT. Lipophilicities as expressed by logD were 0.34 to - 3.80. The selected compounds displayed low protein binding and were stable in PBS and serum. Biodistribution and image contrast in PET/X-ray computed tomography of [. Our studies show the possibility to modify TAFC without losing its properties and specific recognition by A. fumigatus. This opens also new ways for multimodality imaging or theranostics of fungal infection by introducing functionalities such as fluorescent dyes or antifungal moieties.

Topics: Animals; Aspergillus fumigatus; Blood Proteins; Ferric Compounds; Gallium Radioisotopes; Humans; Hydroxamic Acids; Mice, Inbred BALB C; Molecular Imaging; Mutation; Mycoses; Positron Emission Tomography Computed Tomography; Protein Binding; Pulmonary Aspergillosis; Rats; Siderophores; Tissue Distribution

Topics: Animals; Biological Transport; Endocytosis; Ferric Compounds; Fungi; Gallium Radioisotopes; Host-Pathogen Interactions; Humans; Hydroxamic Acids; Iron; Molecular Imaging; Mycoses; Siderophores