TY - JOUR
T1 - Gadolinium chelate safety in pregnancy
T2 - Barely detectable gadolinium levels in the juvenile nonhuman primate after in utero exposure
AU - Prola-Netto, Joao
AU - Woods, Mark
AU - Roberts, Victoria H.J.
AU - Sullivan, Elinor L.
AU - Miller, Christina Ann
AU - Frias, Antonio E.
AU - Oh, Karen Y.
N1 - Funding Information:
Supported by the Bill and Melinda Gates Foundation (OPP1110865) and the National Institutes of Health (P51RR00163, R25EB016671, S10RR025512, UL1TR000128, R01 HD086331, and P51 OD011092).
Funding Information:
Acknowledgments: We thank Katherine Le-wandowski, Tim Frazee, and other members of the animal staff at the Oregon National Primate Research Center for their assistance with the animal procedures. We also thank Matthias C. Schabel, PhD, for his contributions in developing and optimizing the MR imaging data acquisition protocol and for providing the images used in this article. ICPMS measurements were performed by Martina Ralle at the OHSU Elemental Analysis Core, with partial support from National Institutes of Health core grant S10RR025512.
PY - 2018/1
Y1 - 2018/1
N2 - 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 X 10-5 %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 X 10-5 %ID/g; range, [0.81-4.1] X 10-5 %ID/g) and liver (mean, 0.15 X 10-5 %ID/g; range, [0-0.26] X 10-5 %ID/g). Levels were undetectable in the remaining sampled tissues, with the exception of one juvenile skin sample (0.07 X 10-5 %ID/g), one juvenile spleen sample (0.039 X 10-5 %ID/g), and one juvenile brain (0.095 X 10-5 %ID/g) and kidney (0.13 X 10-5 %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.
AB - 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 X 10-5 %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 X 10-5 %ID/g; range, [0.81-4.1] X 10-5 %ID/g) and liver (mean, 0.15 X 10-5 %ID/g; range, [0-0.26] X 10-5 %ID/g). Levels were undetectable in the remaining sampled tissues, with the exception of one juvenile skin sample (0.07 X 10-5 %ID/g), one juvenile spleen sample (0.039 X 10-5 %ID/g), and one juvenile brain (0.095 X 10-5 %ID/g) and kidney (0.13 X 10-5 %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.
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U2 - 10.1148/radiol.2017162534
DO - 10.1148/radiol.2017162534
M3 - Article
C2 - 28873045
AN - SCOPUS:85038921503
SN - 0033-8419
VL - 286
SP - 122
EP - 128
JO - RADIOLOGY
JF - RADIOLOGY
IS - 1
ER -