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

• Published in: Journal of inorganic biochemistry Vol. 186; pp. 176 - 186
• Main Authors: Das, Soma, Parga, Kenia, Chakraborty, Indranil, Tinoco, Arthur D., Delgado, Yamixa, López, Paola M., Fernández Vega, Lauren, Sanakis, Yiannis, Ghosh, Sukhen, Bankson, Jim, Klostergaard, Jim, González-Méndez, Ricardo, Raptis, Raphael G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2018
• Subjects: A549 Cells; Animals; Breast cancer; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - metabolism; Chlorocebus aethiops; Contrast Media - chemical synthesis; Contrast Media - chemistry; Contrast Media - pharmacology; COS Cells; Female; Heterografts; Humans; in vivo study; Iron - chemistry; Iron - pharmacology; Magnetic Resonance Imaging; Mice; Mice, Nude; Molecular relaxivities; MRI; Neoplasm Transplantation; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Paramagnetic contrast agent; Polynuclear iron complex; Molecular relaxivities; Polynuclear iron complex; in vivo study; Breast cancer; MRI; Paramagnetic contrast agent
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2018.06.005

A water-soluble octanuclear cluster, [Fe8], 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 r2 = 4.01, 10.09 and 15.83 mM s−1, respectively. A related hydrophobic [Fe8] cluster conjugated with 5 kDa hyaluronic acid (HA) was characterized by 57Fe-Mössbauer and MALDI-TOF mass spectroscopy, and was evaluated in aqueous solutions in vitro with regard to its contrast enhancing properties [r2 = 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 T2-weighted images (4.7 T) of a human breast cancer xenografted on a nude mouse. The physiologically compatible [Fe8]-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 [Fe8] and its HA-conjugate show a strong magnetic field dependence on r2, rendering them promising platforms for the further development of T2 MRI contrast agents in high and ultrahigh magnetic fields. [Display omitted] •A physiologically accepted, iron-based magnetic resonance imaging (MRI) contrast agent•T2 MRI contrast agent properties of aggregates based on an octanuclear iron-oxo cluster•Study of a hyaluronic acid conjugate of an octanuclear iron cluster•In vitro and in vivo assessment of MRI contrast agent properties