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

J Inorg Biochem. 2018 Sep:186:176-186. doi: 10.1016/j.jinorgbio.2018.06.005. Epub 2018 Jun 26.

Abstract

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.

Keywords: Breast cancer; MRI; Molecular relaxivities; Paramagnetic contrast agent; Polynuclear iron complex; in vivo study.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • A549 Cells
  • Animals
  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / metabolism
  • COS Cells
  • Chlorocebus aethiops
  • Contrast Media* / chemical synthesis
  • Contrast Media* / chemistry
  • Contrast Media* / pharmacology
  • Female
  • Heterografts
  • Humans
  • Iron* / chemistry
  • Iron* / pharmacology
  • Magnetic Resonance Imaging*
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Organometallic Compounds* / chemical synthesis
  • Organometallic Compounds* / chemistry
  • Organometallic Compounds* / pharmacology

Substances

  • Contrast Media
  • Organometallic Compounds
  • Iron