Fe(deferasirox)2: An Iron(III)-Based Magnetic Resonance Imaging T 1 Contrast Agent Endowed with Remarkable Molecular and Functional Characteristics

The search for alternatives to Gd-containing magnetic resonance imaging (MRI) contrast agents addresses the field of Fe­(III)-bearing species with the expectation that the use of an essential metal ion may avoid the issues raised by the exogenous Gd. Attention is currently devoted to highly stable F...

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Veröffentlicht in:Journal of the American Chemical Society 2021-09, Vol.143 (35), p.14178-14188
Hauptverfasser: Palagi, Lorenzo, Di Gregorio, Enza, Costanzo, Diana, Stefania, Rachele, Cavallotti, Camilla, Capozza, Martina, Aime, Silvio, Gianolio, Eliana
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Sprache:eng
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Zusammenfassung:The search for alternatives to Gd-containing magnetic resonance imaging (MRI) contrast agents addresses the field of Fe­(III)-bearing species with the expectation that the use of an essential metal ion may avoid the issues raised by the exogenous Gd. Attention is currently devoted to highly stable Fe­(III) complexes with hexacoordinating ligands, although they may lack any coordinated water molecule. We found that the hexacoordinated Fe­(III) complex with two units of deferasirox, a largely used iron sequestering agent, owns properties that can make it a viable alternative to Gd-based agents. Fe­(deferasirox)2 displays an outstanding thermodynamic stability, a high binding affinity to human serum albumin (three molecules of complex are simultaneously bound to the protein), and a good relaxivity that increases in the range 20–80 MHz. The relaxation enhancement is due to second sphere water molecules likely forming H-bonds with the coordinating phenoxide oxygens. A further enhancement was observed upon the formation of the supramolecular adduct with albumin. The binding sites of Fe­(deferasirox)2 on albumin were characterized by relaxometric competitive assays. Preliminary in vivo imaging studies on a tumor-bearing mouse model indicate that, on a 3 T MRI scanner, the contrast ability of Fe­(deferasirox)2 is comparable to the one shown by the commercial Gd­(DTPA) agent. ICP-MS analyses on blood samples withdrawn from healthy mice administered with a dose of 0.1 mmol/kg of Fe­(deferasirox)2 showed that the complex is completely removed in 24 h.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.1c04963