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长期排泄钆基造影剂:实验性大鼠模型中的线性与大环制剂。

Long-term Excretion of Gadolinium-based Contrast Agents: Linear versus Macrocyclic Agents in an Experimental Rat Model.

机构信息

From the Department of MR and CT Contrast Media Research, Bayer, Muellerstr 178, Berlin 13353, Germany (G.J., T.F., J.L., H.P.); Institute of Physiology, Charité, Berlin, Germany (J.B.); and Forschungszentrum Juelich, Juelich, Germany (V.N.).

出版信息

Radiology. 2019 Feb;290(2):340-348. doi: 10.1148/radiol.2018180135. Epub 2018 Nov 13.

DOI:10.1148/radiol.2018180135
PMID:30422091
Abstract

Purpose To investigate the long-term course of MRI signal intensity (SI) changes and the presence of gadolinium in the rat brain during a 1-year period after multiple administrations of gadolinium-based contrast agents (GBCAs). Materials and Methods Rats received a linear GBCA (gadodiamide, gadopentetate dimeglumine, gadobenate dimeglumine), a macrocyclic GBCA (gadobutrol, gadoterate meglumine, gadoteridol), or saline. Animals received eight injections over 2 weeks (1.8 mmol/kg per injection). Brain MRI and gadolinium measurements were performed with inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS 5, 26, and 52 weeks after administration. Results Animals that received linear GBCAs showed higher deep cerebellar nuclei (DCN)-to-brainstem SI ratios compared with the saline group (P < .001 at all time points). After 1 year, mean gadolinium concentrations in the cerebellum were 3.38 nmol/g (gadodiamide), 2.13 nmol/g (gadopentetate dimeglumine), and 1.91 nmol/g (gadobenate dimeglumine). For linear agents, laser ablation ICP-MS revealed gadolinium depositions in the cerebellar nuclei. For macrocyclic GBCAs, the DCN-to-brainstem SI ratios did not significantly differ from those in the saline group (P > .42) and the cerebellar gadolinium concentrations decreased between weeks 5 and 52, reaching 0.08 nmol/g (gadobutrol), 0.04 nmol/g (gadoterate meglumine), and 0.07 nmol/g (gadoteridol). The respective laser ablation ICP-MS analysis showed no gadolinium depositions. Conclusion Increased signal intensity in the deep cerebellar nuclei of rats persists for at least 1 year after administration of linear gadolinium-based contrast agents (GBCAs), in line with persistent brain gadolinium concentrations with no elimination after the initial 5-week period. The animals that received macrocyclic GBCAs showed an ongoing elimination of gadolinium from the brain during the entire observation period. © RSNA, 2018.

摘要

目的 探究在多次给予基于钆的造影剂(GBCA)后,大鼠脑内 MRI 信号强度(SI)改变及钆存在的长期病程。

材料与方法 大鼠接受线性 GBCA(钆喷酸葡胺、钆喷替酸葡甲胺、钆贝葡胺)、大环 GBCA(钆布醇、钆特酸葡胺、钆特醇)或生理盐水治疗。动物在 2 周内接受 8 次注射(每次 1.8 mmol/kg)。在给药后 5、26 和 52 周进行脑 MRI 和钆测量,采用电感耦合等离子体质谱法(ICP-MS)和激光烧蚀 ICP-MS。

结果 接受线性 GBCA 的动物与生理盐水组相比,深部小脑核(DCN)-脑干 SI 比值更高(所有时间点均 <.001)。1 年后,小脑的平均钆浓度分别为 3.38 nmol/g(钆喷酸葡胺)、2.13 nmol/g(钆喷替酸葡甲胺)和 1.91 nmol/g(钆贝葡胺)。对于线性造影剂,激光烧蚀 ICP-MS 显示在小脑核中存在钆沉积。对于大环 GBCA,DCN-脑干 SI 比值与生理盐水组相比无显著差异(P >.42),且小脑内的钆浓度在 5 周至 52 周之间下降,分别达到 0.08 nmol/g(钆布醇)、0.04 nmol/g(钆特酸葡胺)和 0.07 nmol/g(钆特醇)。相应的激光烧蚀 ICP-MS 分析未显示钆沉积。

结论 大鼠深部小脑核的信号强度在接受线性 GBCA 后至少持续 1 年,与最初 5 周后无消除情况下持续的脑内钆浓度一致。接受大环 GBCA 的动物在整个观察期间表现出脑内钆的持续消除。

© RSNA,2018。

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