Toxicological assessment of gadoversetamide injection (OptiMARK), a new contrast-enhancement agent for use in magnetic resonance imaging

Invest Radiol. 2001 Jul;36(7):401-12. doi: 10.1097/00004424-200107000-00006.


Rationale and objectives: A series of preclinical tests were undertaken during the developmental process to determine the safety profile of gadoversetamide injection (OptiMARK).

Methods: Acute intravenous, acute intracisternal, and repeated-dose toxicities; cardiovascular effects; and genetic and reproductive toxicology characteristics were assessed in several animal species.

Results: Gadoversetamide injection demonstrated an acute intravenous median lethal dose of 25 to 28 mmol/kg and a maximum nonlethal dose of 14 mmol/kg in mice. In the dog, acute administration of gadoversetamide injection showed a no observable effect level at 3 mmol/kg. Dosed daily for 4 weeks, gadoversetamide injection (0.1 mmol x kg(-1) x d(-1)) caused no serious irreversible changes in any organs in rats and dogs. At a dose of 0.1 mmol/kg, gadoversetamide injection caused no significant (P < 0.05) changes in cardiovascular function in anesthetized dogs. Gadoversetamide injection showed no mutagenic activity. Fertility, reproductive performance, and postnatal fetal development were not affected at doses up to 0.5 mmol x kg(-1) x d(-1) in the rat. No teratogenicity was observed at doses up to 4.2 mmol x kg(-1) x d(-1) in the rat and up to 1.6 mmol x kg(-1) x d(-1) in the rabbit.

Conclusions: Data from our toxicological assessment demonstrate the safety of gadoversetamide injection in a number of animal species at doses exceeding the intended human clinical dose.

MeSH terms

  • Abnormalities, Drug-Induced
  • Animals
  • Blood Cells
  • Cardiovascular System / drug effects
  • Contrast Media / administration & dosage
  • Contrast Media / toxicity*
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Female
  • Fertility / drug effects
  • Fetus / drug effects
  • Injections, Intravenous
  • Lethal Dose 50
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mutagenesis / drug effects
  • Mutagenesis / genetics
  • Organometallic Compounds / administration & dosage
  • Organometallic Compounds / toxicity*
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Toxicity Tests


  • Contrast Media
  • Organometallic Compounds
  • gadoversetamide