Cellular internalization and morphological analysis after intravenous injection of a highly hydrophilic octahedral rhenium cluster complex - a new promising X-ray contrast agent

Contrast Media Mol Imaging. 2016 Nov;11(6):459-466. doi: 10.1002/cmmi.1707. Epub 2016 Aug 4.

Abstract

The octahedral cluster compound Na2 H8 [{Re6 Se8 }(P(C2 H4 CONH2 )(C2 H4 COO)2 )6 ] has been shown to be highly radio dense, thus becoming a promising X-ray contrast agent. It was also shown that this compound had low cytotoxic effect in vitro, low acute toxicity in vivo and was eliminated rapidly from the body through the urinary tract. The present contribution describes a more detailed cellular internalization assay and morphological analysis after intravenous injection of this hexarhenium cluster compound at different doses. The median lethal dose (LD50 ) of intravenously administrated compound was calculated (4.67 ± 0.69 g/kg). Results of the study clearly indicated that the cluster complex Hn [{Re6 Se8 }(P(C2 H4 CONH2 )(C2 H4 COO)2 )6 ]n-10 was not internalized into cells in vitro and induced only moderate morphological alterations of kidneys at high doses without any changes in morphology of liver, spleen, duodenum, or heart of mice. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: acute intravenous toxicity; cellular internalization; drug development; octahedral rhenium cluster complex; safety assessment; vascular contrast agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Membrane / metabolism*
  • Cell Shape / drug effects
  • Contrast Media / administration & dosage
  • Contrast Media / chemistry
  • Contrast Media / pharmacokinetics*
  • Contrast Media / toxicity
  • Coordination Complexes / administration & dosage
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacokinetics*
  • Coordination Complexes / toxicity
  • Duodenum / drug effects
  • Duodenum / pathology
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Injections, Intravenous
  • Kidney / drug effects
  • Kidney / pathology
  • Lethal Dose 50
  • Liver / drug effects
  • Liver / pathology
  • Mice
  • Myocardium / pathology
  • Rhenium / chemistry*
  • Rhenium / toxicity
  • Spleen / drug effects
  • Spleen / pathology
  • X-Rays

Substances

  • Contrast Media
  • Coordination Complexes
  • Rhenium