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 ICP-MS analyses on blood samples withdrawn from healthy mice administered with a dose of 0.1 mmol/kg of Fe(deferasirox)2 showed that the complex is completely removed in 24 h.
Fe(deferasirox)2: An Iron(III)-Based Magnetic Resonance Imaging T1Contrast Agent Endowed with Remarkable Molecular and Functional Characteristics
Palagi L.First
;Di Gregorio E.;Costanzo D.;Stefania R.;Capozza M.;Aime S.;Gianolio E.
2021-01-01
Abstract
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.
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