The Effect of Perinatal Gadolinium-Based Contrast Agents on Adult Mice Behavior

Invest Radiol. 2018 Feb;53(2):110-118. doi: 10.1097/RLI.0000000000000417.

Abstract

Objectives: The aim of this study was to examine the effects of perinatal exposure to gadolinium (Gd)-based contrast agents (GBCAs) on the behavior of adulthood offspring.

Materials and methods: Pregnant Balb/C mice (n = 5 per group) were intravenously injected with gadoterate meglumine (Magnescope, macrocyclic GBCA), gadodiamide (Omniscan, linear GBCA), or vehicle from pregnancy day 15 to 19, corresponding to embryonic day 15 to 19 of the fetus, at 2 mmol/kg body weight per day. Brain samples from dams and pups were collected on postpartum day 28. The total Gd concentration was quantified by inductively coupled plasma-mass spectrometry (dams, n = 3; gadoterate meglumine-treated pups group, n = 9; and gadodiamide-treated pups group, n = 10). Behavioral testing of offspring was started on postpartum day 70 (control group, n = 22; gadoterate meglumine-treated group, n = 23; and gadodiamide-treated group, n = 20).

Results: Higher levels of Gd retention were observed in dams and pups in the gadodiamide-treated group. Perinatal exposure to GBCAs caused anxiety-like behavior, disrupted motor coordination, impaired memory function, stimulated tactile sensitivity, and decreased muscle strength, particularly in the gadodiamide-treated group.

Conclusions: In the present study, we showed that Gd was transferred to pups and was retained in their brain during postnatal development. Gadolinium retention may lead to impaired brain development. These findings indicate that the use of GBCAs in pregnant women should be avoided because it may have adverse effects on the fetus, particularly on brain development.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Brain / drug effects
  • Contrast Media / administration & dosage
  • Contrast Media / adverse effects
  • Contrast Media / pharmacology*
  • Disease Models, Animal
  • Female
  • Gadolinium / adverse effects
  • Gadolinium / pharmacology*
  • Gadolinium DTPA / adverse effects
  • Gadolinium DTPA / pharmacology*
  • Humans
  • Male
  • Meglumine / adverse effects
  • Meglumine / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Organometallic Compounds / adverse effects
  • Organometallic Compounds / pharmacology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Spectrophotometry, Atomic

Substances

  • Contrast Media
  • Organometallic Compounds
  • Meglumine
  • gadodiamide
  • Gadolinium
  • Gadolinium DTPA
  • gadoterate meglumine