Magnetic resonance imaging contrast enhancement in vitro and in vivo by octanuclear iron-oxo cluster-based agents

A water-soluble octanuclear cluster, [Fe 8 ], was studied with regard to its properties as a potential contrast enhancing agent in magnetic resonance imaging (MRI) in magnetic fields of 1.3, 7.2 and 11.9 T and was shown to have transverse relaxivities r 2 = 4.01, 10.09 and 15.83 mM s −1 , respectively. A related hydrophobic [Fe 8 ] cluster conjugated with 5 kDa hyaluronic acid (HA) was characterized by 57 Fe-Mossbauer and MALDI-TOF mass spectroscopy, and was evaluated in aqueous solutions in vitro with regard to its contrast enhancing properties [r 2 = 3.65 mM s −1 (1.3 T), 26.20 mM s −1 (7.2 T) and 52.18 mM s −1 (11.9 T)], its in vitro cellular cytotoxicity towards A-549 cells and COS-7 cells and its in vivo enhancement of T 2 -weighted images (4.7 T) of a human breast cancer xenografted on a nude mouse. The physiologically compatible [Fe 8 ]-HA conjugate was i.v. injected to the tumor-bearing mouse, resulting in observable, heterogeneous signal change within the tumor, evident 15 min after injection and persisting for approximately 30 min. Both molecular [Fe 8 ] and its HA-conjugate show a strong magnetic field dependence on r 2 , rendering them promising platforms for the further development of T 2 MRI contrast agents in high and ultrahigh magnetic fields.