Towards An Advanced Graphene-Based Magnetic Resonance Imaging Contrast Agent: Sub-acute Toxicity and Efficacy Studies in Small Animals

Sci Rep. 2015 Dec 2:5:17182. doi: 10.1038/srep17182.

Abstract

Current clinical Gd(3+)-based T1 magnetic resonance imaging (MRI) contrast agents (CAs) are suboptimal or unsuitable, especially at higher magnetic fields (>1.5 Tesla) for advanced MRI applications such as blood pool, cellular and molecular imaging. Herein, towards the goal of developing a safe and more efficacious high field T1 MRI CA for these applications, we report the sub-acute toxicity and contrast enhancing capabilities of a novel nanoparticle MRI CA comprising of manganese (Mn(2+)) intercalated graphene nanoparticles functionalized with dextran (hereafter, Mangradex) in rodents. Sub-acute toxicology performed on rats intravenously injected with Mangradex at 1, 50 or 100 mg/kg dosages 3 times per week for three weeks indicated that dosages ≤50 mg/kg could serve as potential diagnostic doses. Whole body 7 Tesla MRI performed on mice injected with Mangradex at a potential diagnostic dose (25 mg/kg or 455 nanomoles Mn(2+)/kg; ~2 orders of magnitude lower than the paramagnetic ion concentration in a typical clinical dose) showed persistent (up to at least 2 hours) contrast enhancement in the vascular branches (Mn(2+) concentration in blood at steady state = 300 ppb, per voxel = 45 femtomoles). The results lay the foundations for further development of Mangradex as a vascular and cellular/ molecular MRI probe.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media* / adverse effects
  • Contrast Media* / pharmacokinetics
  • Contrast Media* / pharmacology
  • Female
  • Gadolinium / adverse effects
  • Gadolinium / pharmacokinetics
  • Gadolinium / pharmacology
  • Graphite* / adverse effects
  • Graphite* / pharmacokinetics
  • Graphite* / pharmacology
  • Magnetic Resonance Imaging / methods*
  • Male
  • Manganese* / adverse effects
  • Manganese* / pharmacokinetics
  • Manganese* / pharmacology
  • Mice
  • Nanoparticles*
  • Rats
  • Rats, Wistar

Substances

  • Contrast Media
  • Manganese
  • Graphite
  • Gadolinium