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钆螯合物在孕期的安全性:子宫内暴露后幼年非人灵长类动物体内钆水平几乎检测不到

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

作者信息

Prola-Netto Joao, Woods Mark, Roberts Victoria H J, Sullivan Elinor L, Miller Christina Ann, Frias Antonio E, Oh Karen Y

机构信息

From the Departments of Radiology (J.P.N., K.Y.O.), Neurology (J.P.N.), and Obstetrics and Gynecology, Division of Maternal Fetal Medicine (A.E.F.), and Advanced Imaging Research Center (M.W.), Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Room L603, Portland, OR 97239; Divisions of Reproductive and Developmental Sciences (V.H.J.R., A.E.F.) and Neurosciences (E.L.S.), Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Ore; and Department of Chemistry, Portland State University, Portland, Ore (M.W., C.A.M.).

出版信息

Radiology. 2018 Jan;286(1):122-128. doi: 10.1148/radiol.2017162534. Epub 2017 Sep 4.

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.

摘要

目的 确定孕期母体静脉注射钆特醇后,钆是否会留存于幼年非人灵长类动物组织中。材料与方法 在机构动物护理与使用委员会批准下,饲养妊娠恒河猴及其后代(n = 10)。作为一项已有的正在进行的研究方案的一部分,对它们进行前瞻性研究,以评估母体营养不良对胎盘和胎儿发育的影响。在妊娠第85天和第135天,静脉注射钆特醇后对它们进行胎盘磁共振成像检查。在第135天给予第二剂钆特醇之前进行羊膜穿刺术。分娩后,对后代进行7个月的随访。从每只幼年猕猴采集来自八个不同器官和血液的组织样本。使用电感耦合等离子体质谱法测量钆水平。结果 注射一剂钆特醇50天后,羊水中钆浓度为0.028×10%ID/g(每克组织的注射剂量百分比)。钆在股骨中最常被检测到(平均值,2.5×10%ID/g;范围,[0.81 - 4.1]×10%ID/g)和肝脏(平均值,0.15×10%ID/g;范围,[0 - 0.26]×10%ID/g)。除一个幼年皮肤样本(0.07×10%ID/g)、一个幼年脾脏样本(0.039×10%ID/g)、一个幼年脑(0.095×10%ID/g)和肾脏(0.13×10%ID/g)样本外,其余采样组织中均未检测到钆水平。结论 母体注射后羊水中存在钆特醇,证实其可穿过胎盘。子宫内暴露于两剂钆特醇后,幼年猕猴组织中发现极低水平的钆,表明分娩后仅有极少量钆留存。RSNA,2017年。

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