Gadolinium Retention in the Rat Brain: Assessment of the Amounts of Insoluble Gadolinium-containing Species and Intact Gadolinium Complexes after Repeated Administration of Gadolinium-based Contrast Agents

Gadolinium Retention in the Rat Brain: Assessment of the Amounts of Insoluble Gadolinium-containing Species and Intact Gadolinium Complexes after Repeated Administration of Gadolinium-based Contrast Agents
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DOI:
10.1148/radiol.2017162857
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发表时间:
2017-12-01
期刊:
影响因子:
19.7
通讯作者:
Aime, Silvio
Aime, Silvio
中科院分区:
医学1区
文献类型:
--
作者:
Gianolio, Eliana;Bardini, Paola;Aime, Silvio

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目的:为了评估含钆物种的形态后,多次管理的钆为基础的造影剂(GBCA)钆双胺和钆特醇,并量化完整的钆络合物和不溶性钆含species.Materials and Methods的量:总剂量为13.2 mmol每公斤体重的每个GBCA在一段时间内的健康Wistar大鼠8周。最后一次给药后3天,处死大鼠,切除脑并分成3部分。将每份脑匀浆分成两部分,一部分用于用电感耦合等离子体质谱法测定总钆浓度,另一部分用于测定完整GBCA和含钆不溶性物质的量。还进行了在聚唾液酸存在下钆双胺和钆双胺的弛豫测量。钆双胺和钆特醇的平均总钆浓度分别为0.317 μ g/g +/- 0.060(标准差)和0.048 μ g/g +/- 0.004,皮质下脑中分别为0.418 μ g/g +/- 0.078和0.051 μ g/g +/- 0.009,小脑为0.781 μ g/g ± 0.079和0.061 μ g/g ± 0.012。钆特醇包含100%在接受钆特醇给药的大鼠中发现的钆物质。在接受钆双胺治疗的大鼠中,保留在脑组织中的大部分钆是不溶性物质。在小脑中,完整钆双胺的量占其中发现的总钆的18.2% +/-10.6%。钆的质量平衡表明存在其他可溶性含钆物质(约30%)。在1.5 T和298 K下,在体外形成的钆聚唾液酸物质的弛豫率为97.8 mM/sec。结论:钆特醇保留得少得多,并且整个检测到的钆是完整的可溶性GBCA,而钆双胺产生可溶性和不溶性含钆物质,其中不溶性物质占主导地位。(C)RSNA,2017
Purpose: To evaluate the speciation of gadolinium-containing species after multiple administrations of the gadolinium-based contrast agents (GBCAs) gadodiamide and gadoteridol and to quantify the amount of intact gadolinium complexes and insoluble gadolinium-containing species.Materials and Methods: A total dose of 13.2 mmol per kilogram of body weight of each GBCA was administered in healthy Wistar rats over a period of 8 weeks. Three days after the final administration, rats were sacrificed, and the brains were excised and divided into three portions. Each portion of brain homogenate was divided into two parts, one for determination of the total gadolinium concentration with inductively coupled plasma mass spectrometry and one for determination of the amount of intact GBCA and gadolinium-containing insoluble species. Relaxometric measurements of gadodiamide and gadolinium trichloride in the presence of polysialic acid were also performed.Results: The mean total gadolinium concentrations for gadodiamide and gadoteridol, respectively, were 0.317 mu g/g +/- 0.060 (standard deviation) and 0.048 mu g/g +/- 0.004 in the cortex, 0.418 mu g/g +/- 0.078 and 0.051 mu g/g +/- 0.009 in the subcortical brain, and 0.781 mu g/g +/- 0.079 and 0.061 mu g/g +/- 0.012 in the cerebellum. Gadoteridol comprised 100% of the gadolinium species found in rats treated with gadoteridol. In rats treated with gadodiamide, the largest part of gadolinium retained in brain tissue was insoluble species. In the cerebellum, the amount of intact gadodiamide accounts for 18.2% +/- 10.6 of the total gadolinium found therein. The mass balance found for gadolinium implies the occurrence of other soluble gadolinium- containing species (approximately 30%). The relaxivity of the gadolinium polysialic acid species formed in vitro was 97.8 mM/sec at 1.5 T and 298 K.Conclusion: Gadoteridol was far less retained, and the entire detected gadolinium was intact soluble GBCA, while gadodiamide yielded both soluble and insoluble gadolinium-containing species, with insoluble species dominating. (C) RSNA, 2017