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-Mössbauer 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.