Desferoxamine (DFO) is currently the golden standard chelator for 89Zr4+, a promising nuclide for positron emission tomography imaging (PET). The natural siderophore DFO had previously been conjugated with fluorophores to obtain Fe(III) sensing molecules. In this study, a fluorescent coumarin derivative of DFO (DFOC) has been prepared and characterized (potentiometry, UV–Vis spectroscopy) for what concerns its protonation and metal coordination properties towards PET-relevant ions (Cu(II), Zr(IV)), evidencing strong similarity with pristine DFO. Retention of DFOC fluorescence emission upon metal binding has been checked (fluorescence spectrophotometry), as it would – and does – allow for optical (fluorescent) imaging, thus unlocking bimodal (PET/fluorescence) imaging for 89Zr(IV) tracers. Crystal violet and MTT assays on NIH-3 T3 fibroblasts and MDA-MB 231 mammary adenocarcinoma cell lines demonstrated, respectively, no cytotoxicity nor metabolic impairment at usual radiodiagnostic concentrations of ZrDFOC. Clonogenic colony-forming assay performed on X-irradiated MDA-MB 231 cells showed no interference of ZrDFOC with radiosensitivity. Morphological biodistribution (confocal fluorescence, transmission electron microscopy) assays on the same cells suggested internalization of the complex through endocytosis. Overall, these results support fluorophore-tagged DFO as a suitable option to achieve dual imaging (PET/fluorescence) probes based on 89Zr.

Evaluation of coumarin-tagged deferoxamine as a Zr(IV)-based PET/fluorescence dual imaging probe / Giammarco Maria Romano, Virginia Zizi, Giulia Salvatore, Riccardo Bani, Monica Mangoni, Silvia Nistri, Giulia Anichini, Yschtar Tecla Simonini Steiner, Daniele Bani, Antonio Bianchi, Andrea Bencini, Matteo Savastano. - In: JOURNAL OF INORGANIC BIOCHEMISTRY. - ISSN 0162-0134. - ELETTRONICO. - 245:(2023), pp. 112259.0-112259.0. [10.1016/j.jinorgbio.2023.112259]

Evaluation of coumarin-tagged deferoxamine as a Zr(IV)-based PET/fluorescence dual imaging probe

Giammarco Maria Romano
Membro del Collaboration Group
;
Virginia Zizi
Membro del Collaboration Group
;
Giulia Salvatore
Membro del Collaboration Group
;
Monica Mangoni
Membro del Collaboration Group
;
Silvia Nistri
Membro del Collaboration Group
;
Giulia Anichini
Membro del Collaboration Group
;
Yschtar Tecla Simonini Steiner
Membro del Collaboration Group
;
Daniele Bani
Membro del Collaboration Group
;
Antonio Bianchi
Membro del Collaboration Group
;
Andrea Bencini
Membro del Collaboration Group
;
Matteo Savastano
Membro del Collaboration Group
2023

Abstract

Desferoxamine (DFO) is currently the golden standard chelator for 89Zr4+, a promising nuclide for positron emission tomography imaging (PET). The natural siderophore DFO had previously been conjugated with fluorophores to obtain Fe(III) sensing molecules. In this study, a fluorescent coumarin derivative of DFO (DFOC) has been prepared and characterized (potentiometry, UV–Vis spectroscopy) for what concerns its protonation and metal coordination properties towards PET-relevant ions (Cu(II), Zr(IV)), evidencing strong similarity with pristine DFO. Retention of DFOC fluorescence emission upon metal binding has been checked (fluorescence spectrophotometry), as it would – and does – allow for optical (fluorescent) imaging, thus unlocking bimodal (PET/fluorescence) imaging for 89Zr(IV) tracers. Crystal violet and MTT assays on NIH-3 T3 fibroblasts and MDA-MB 231 mammary adenocarcinoma cell lines demonstrated, respectively, no cytotoxicity nor metabolic impairment at usual radiodiagnostic concentrations of ZrDFOC. Clonogenic colony-forming assay performed on X-irradiated MDA-MB 231 cells showed no interference of ZrDFOC with radiosensitivity. Morphological biodistribution (confocal fluorescence, transmission electron microscopy) assays on the same cells suggested internalization of the complex through endocytosis. Overall, these results support fluorophore-tagged DFO as a suitable option to achieve dual imaging (PET/fluorescence) probes based on 89Zr.
2023
245
0
0
Giammarco Maria Romano, Virginia Zizi, Giulia Salvatore, Riccardo Bani, Monica Mangoni, Silvia Nistri, Giulia Anichini, Yschtar Tecla Simonini Steiner...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1311404
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