{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:51:51Z","timestamp":1790675511928,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P 30924-B26"],"award-info":[{"award-number":["P 30924-B26"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004955","name":"\u00d6sterreichische Forschungsf\u00f6rderungsgesellschaft","doi-asserted-by":"publisher","award":["BioNMR858017"],"award-info":[{"award-number":["BioNMR858017"]}],"id":[{"id":"10.13039\/501100004955","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ENOCH","award":["CZ.02.1.01\/0.0\/0.0\/16_019\/0000868"],"award-info":[{"award-number":["CZ.02.1.01\/0.0\/0.0\/16_019\/0000868"]}]},{"DOI":"10.13039\/501100001824","name":"Grantov\u00e1 Agentura \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["19-10907S"],"award-info":[{"award-number":["19-10907S"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Invasive pulmonary aspergillosis (IPA) is a life-threatening form of fungal infection, primarily in immunocompromised patients and associated with significant mortality. Diagnostic procedures are often invasive and\/or time consuming and existing antifungals can be constrained by dose-limiting toxicity and drug interaction. In this study, we modified triacetylfusarinine C (TAFC), the main siderophore produced by the opportunistic pathogen Aspergillus fumigatus (A. fumigatus), with antifungal molecules to perform antifungal susceptibility tests and molecular imaging. A variation of small organic molecules (eflornithine, fludioxonil, thiomersal, fluoroorotic acid (FOA), cyanine 5 (Cy5) with antifungal activity were coupled to diacetylfusarinine C (DAFC), resulting in a \u201cTrojan horse\u201d to deliver antifungal compounds specifically into A. fumigatus hyphae by the major facilitator transporter MirB. Radioactive labeling with gallium-68 allowed us to perform in vitro characterization (distribution coefficient, stability, uptake assay) as well as biodistribution experiments and PET\/CT imaging in an IPA rat infection model. Compounds chelated with stable gallium were used for antifungal susceptibility tests. [Ga]DAFC-fludioxonil, -FOA, and -Cy5 revealed a MirB-dependent active uptake with fungal growth inhibition at 16 \u00b5g\/mL after 24 h. Visualization of an A. fumigatus infection in lungs of a rat was possible with gallium-68-labeled compounds using PET\/CT. Heterogeneous biodistribution patterns revealed the immense influence of the antifungal moiety conjugated to DAFC. Overall, novel antifungal siderophore conjugates with promising fungal growth inhibition and the possibility to perform PET imaging combine both therapeutic and diagnostic potential in a theranostic compound for IPA caused by A. fumigatus.<\/jats:p>","DOI":"10.3390\/jof7070558","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T10:13:42Z","timestamp":1626257622000},"page":"558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Antifungal Siderophore Conjugates for Theranostic Applications in Invasive Pulmonary Aspergillosis Using Low-Molecular TAFC Scaffolds"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5357-126X","authenticated-orcid":false,"given":"Joachim","family":"Pfister","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Medical University Innsbruck, A-6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1334-5916","authenticated-orcid":false,"given":"Milos","family":"Petrik","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, 77200 Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6681-0100","authenticated-orcid":false,"given":"Katerina","family":"Bendova","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, 77200 Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4507-8739","authenticated-orcid":false,"given":"Barbara","family":"Matuszczak","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy\/Pharmaceutical Chemistry, University of Innsbruck, A-6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2160-2903","authenticated-orcid":false,"given":"Ulrike","family":"Binder","sequence":"additional","affiliation":[{"name":"Institute of Hygiene & Medical Microbiology, Medical University of Innsbruck, A-6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6380-700X","authenticated-orcid":false,"given":"Matthias","family":"Misslinger","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, Medical University of Innsbruck, A-6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4672-0217","authenticated-orcid":false,"given":"Alexander","family":"K\u00fchbacher","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, Medical University of Innsbruck, A-6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9257-8648","authenticated-orcid":false,"given":"Fabio","family":"Gsaller","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, Medical University of Innsbruck, A-6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2472-9878","authenticated-orcid":false,"given":"Hubertus","family":"Haas","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, Medical University of Innsbruck, A-6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0566-4036","authenticated-orcid":false,"given":"Clemens","family":"Decristoforo","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical University Innsbruck, A-6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bongomin, F., Gago, S., Oladele, R., and Denning, D. 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