Achieving Biocompatible SABRE: An in vitro Cytotoxicity Study

ChemMedChem. 2018 Feb 20;13(4):352-359. doi: 10.1002/cmdc.201700725. Epub 2018 Jan 18.

Abstract

Production of a biocompatible hyperpolarized bolus for signal amplification by reversible exchange (SABRE) could open the door to simple clinical diagnosis via magnetic resonance imaging. Essential to successful progression to preclinical/clinical applications is the determination of the toxicology profile of the SABRE reaction mixture. Herein, we exemplify the cytotoxicity of the SABRE approach using in vitro cell assays. We conclude that the main cause of the observed toxicity is due to the SABRE catalyst. We therefore illustrate two catalyst removal methods: one involving deactivation and ion-exchange chromatography, and the second using biphasic catalysis. These routes produce a bolus suitable for future in vivo study.

Keywords: SABRE; biocompatibility; biphasic catalysis; cytotoxicity; hyperpolarization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Catalysis
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coordination Complexes / chemistry
  • Coordination Complexes / toxicity*
  • Humans
  • Iridium / chemistry*
  • Nicotinic Acids / metabolism
  • Nicotinic Acids / toxicity
  • Solvents / chemistry
  • Toxicity Tests*

Substances

  • Biocompatible Materials
  • Coordination Complexes
  • Nicotinic Acids
  • Solvents
  • Iridium
  • methyl nicotinate