Gadolinium Chelate Safety in Pregnancy: Barely Detectable Gadolinium Levels in the Juvenile Nonhuman Primate after in Utero Exposure

Abstract

Purpose To determine whether gadolinium remains in juvenile nonhuman primate tissue after maternal exposure to intravenous gadoteridol during pregnancy. Materials and Methods Gravid rhesus macaques and their offspring (n = 10) were maintained, as approved by the institutional animal care and utilization committee. They were prospectively studied as part of a pre-existing ongoing research protocol to evaluate the effects of maternal malnutrition on placental and fetal development. On gestational days 85 and 135, they underwent placental magnetic resonance imaging after intravenous gadoteridol administration. Amniocentesis was performed on day 135 prior to administration of the second dose of gadoteridol. After delivery, the offspring were followed for 7 months. Tissue samples from eight different organs and from blood were harvested from each juvenile macaque. Gadolinium levels were measured by using inductively coupled plasma mass spectrometry. Results Gadolinium concentration in the amniotic fluid was 0.028 × 10 %ID/g (percentage injected dose per gram of tissue) 50 days after administration of one gadoteridol dose. Gadolinium was most consistently detected in the femur (mean, 2.5 × 10 %ID/g; range, [0.81-4.1] × 10 %ID/g) and liver (mean, 0.15 × 10 %ID/g; range, [0-0.26] × 10 %ID/g). Levels were undetectable in the remaining sampled tissues, with the exception of one juvenile skin sample (0.07 × 10 %ID/g), one juvenile spleen sample (0.039 × 10 %ID/g), and one juvenile brain (0.095 × 10 %ID/g) and kidney (0.13 × 10 %ID/g) sample. Conclusion The presence of gadoteridol in the amniotic fluid after maternal injection enables confirmation that it crosses the placenta. Extremely low levels of gadolinium are found in juvenile macaque tissues after in utero exposure to two doses of gadoteridol, indicating that a very small amount of gadolinium persists after delivery. RSNA, 2017.

Perfusion of the placenta assessed using arterial spin labeling and ferumoxytol dynamic contrast enhanced magnetic resonance imaging in the rhesus macaque

“…However, most GBCAs exchange with the extravascular space. Recently, GBCAs were shown to be at nearly undetectable levels in the fetal and placental tissue in nonhuman primates after intravenous infusion for DCE MRI, but they have previously been observed in the bladder of the fetus . Ferumoxytol can be administered during pregnancy similar to other intravenous iron preparations, but is safer and produces fewer allergic and idiosyncratic reactions .…”

Detection and imaging of gadolinium accumulation in human bone tissue by micro- and submicro-XRF

“…Interesting results showing differential accumulation of Gd by different bone tissues -cortical, trabecular bone and bone marrow in juvenile and adult rats by ICP-MS were published by Fretellier et al 48 . An interesting line of research -usage of GBCAs in pregnancy and potential effect of Gd on foetus, were investigated by Prola-Netto et al in rhesus macaques, and although only extremely low levels of Gd were found in juvenile tissues after in utero exposure, femur was identified as a site of consistent Gd retention in all the animals 49 . Until now, however, the studies allowing elucidation of mechanisms of Gd incorporation into bone, as well as its further fate, were not undertaken, therefore, animal models and studies involving human biopsies are called for 50 .…”

Gadolinium deposition and the potential for toxicological sequelae – A literature review of issues surrounding gadolinium‐based contrast agents

“…This may result in mitochondrial dysfunction with gestational and early‐age exposure to La 3+ ions, causing impaired spatial learning and memory in young rats . GBCAs have been shown to cross the placenta in nonhuman primates, with juvenile macaques having low levels of up to 0.000025% of the injected dose of gadolinium present in multiple tissues, particularly in the femur, but also in the liver following in utero exposure to via placental MRI after intravenous gadoteridol (macrocyclic) administration on gestational days 85 and 135 . Whether this has implications for human pregnancies is unclear.…”