Modifying the Siderophore Triacetylfusarinine C for Molecular Imaging of Fungal Infection.
Purpose: 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 [68Ga]TAFC ex...
| Published in: | Molecular Imaging & Biology Vol. 21; no. 6; pp. 1097 - 1107 |
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| Main Authors: | , , , , , , , , , , |
| Format: | diagnostic images pictorial research tables/charts Journal Article |
| Published: |
Springer Nature
Dec2019
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=139744977&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 139744977 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 15361632 KJU jtl: Molecular Imaging & Biology issn: 15361632 maglogo: N pubinfo: dt: Dec2019 vid: 21 iid: 6 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 139744977 139744977 144159548 NLM30838551 139744977 10.1007/s11307-019-01325-6 NLM30838551 139744977 ppf: 1097 ppct: 10 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Modifying the Siderophore Triacetylfusarinine C for Molecular Imaging of Fungal Infection. aug: au: Kaeopookum, Piriya Summer, Dominik Pfister, Joachim Orasch, Thomas Lechner, Beatrix E. Petrik, Milos Novy, Zbynek Matuszczak, Barbara Rangger, Christine Haas, Hubertus Decristoforo, Clemens affil: Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria sug: subj: Hydroxy Acids Chelating Agents Ferric Compounds Mycoses Molecular Imaging Pulmonary Aspergillosis Aspergillus Physiology Gallium Radioisotopes Animal Studies Rats Mycoses Microbiology Pulmonary Aspergillosis Microbiology Mice Human Mutation Blood Proteins Metabolism Validation Studies Comparative Studies Evaluation Research Multicenter Studies Funding Source ab: Purpose: 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 [68Ga]TAFC exhibited excellent targeting properties in an A. fumigatus rat infection model. In this study, we aimed to prepare TAFC analogs modifying fusarinine C (FSC) by acylation with different carbon chain lengths as well as with charged substituents and investigated the influence of introduced substituents on preservation of TAFC characteristics in vitro and in vivo.Procedures: 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, [68Ga]tripropanoyl(FSC) ([68Ga]TPFC), [68Ga]diacetylbutanoyl(FSC) ([68Ga]DABuFC), and [68Ga]trisuccinyl(FSC) ([68Ga]FSC(suc)3), with high, medium, and low in vitro uptake in fungal cultures, were selected for further evaluation. Stability and protein binding were evaluated and in vivo imaging performed in the A. fumigatus rat infection model.Results: 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 [68Ga]TPFC and [68Ga]DABuFC were comparable to [68Ga]TAFC, whereas no uptake in the infected region was observed with [68Ga]FSC(suc)3.Conclusions: 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. pubtype: Academic Journal doctype: diagnostic images pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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