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医源性镧和钆在人体内的沉积模式取决于所输送的化学结合形式。

Deposition patterns of iatrogenic lanthanum and gadolinium in the human body depend on delivered chemical binding forms.

机构信息

Institute of Inorganic and Analytical Chemistry, University of Münster, 48149 Münster, Germany.

Diagnostic Imaging Research Unit (DIRU), Clinic for Diagnostic Imaging, University of Zurich, CH-8057 Zurich, Switzerland.

出版信息

J Trace Elem Med Biol. 2021 Jan;63:126665. doi: 10.1016/j.jtemb.2020.126665. Epub 2020 Oct 24.

Abstract

BACKGROUND

Recently, gadolinium from linear GBCAs has been reported to deposit in various regions of the body. Besides gadolinium, other lanthanides are used in medical care. In the current study, we investigated deposition of lanthanum in two patients who received lanthanum carbonate as a phosphate binder due to chronic kidney injury and compared it to additionally found Gd deposition.

METHODS

Tissue specimens of two patients with long-term application of lanthanum carbonate as well as possible GBCA application were investigated. Spatial distribution of gadolinium and lanthanum was determined by quantitative laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging of tissue sections. The deposition of gadolinium and lanthanum in different organs was compared, and the ratio of Gd concentration to La concentration (Gd-to-La-ratio) was investigated on an individual pixel base within the images.

RESULTS

Deposition of Gd and La was found in all investigated tissues of both patients. Gd and La exhibited high spatial correlation for all samples, with the main deposition being located in the middle coat (tunica media) of blood vessels. The Gd-to-La-ratio was similar in the tissues investigated (between 8 ± 4 (mean ± standard deviation) and 10 ± 2), except for the thyroid vasculature and surrounding tissue (90 ± 17) as well as the cerebellum (270 ± 18). Here, the ratio was significantly increased towards higher Gd concentration.

CONCLUSION

The results of this study demonstrate long-term deposition of La and comparable localization of additionally found Gd in various tissues of the body. La deposition was relatively low, considering the total administered amount of lanthanum carbonate of up to 11.5 kg, indicating a low absorption and/or high excretion of lanthanum. However, the total amount of deposited La is significant and raises questions about possible adverse side effects. The ratio-approach allows for the usage of the additionally generated Gd data, without detailed knowledge about possible GBCA applications. The significantly decreased Gd-to-La-ratio in the brain might be explained by the lanthanum being released and taken up as free La ion in the stomach that impedes a crossing of the blood-brain-barrier while the intravenously injected GBCAs might dechelate first when they have already crossed the blood-brain-barrier.

摘要

背景

最近,线性 GBCA 中的钆已被报道会在体内的各个部位沉积。除了钆之外,其他镧系元素也被用于医疗护理。在本研究中,我们调查了两名因慢性肾损伤而接受碳酸镧作为磷酸盐结合剂治疗的患者的镧沉积情况,并将其与额外发现的 Gd 沉积进行了比较。

方法

对两名长期应用碳酸镧且可能应用 GBCA 的患者的组织标本进行了研究。通过对组织切片进行定量激光烧蚀-电感耦合等离子体质谱(LA-ICP-MS)成像,确定了钆和镧的空间分布。比较了不同器官中镧和钆的沉积情况,并在图像的单个像素基础上研究了 Gd 浓度与 La 浓度的比值(Gd-to-La-ratio)。

结果

两名患者的所有研究组织中均发现了 Gd 和 La 的沉积。所有样本中 Gd 和 La 均表现出高度的空间相关性,主要沉积位于血管的中膜(中层)。在所研究的组织中,Gd-to-La-ratio 相似(在 8 ± 4(平均值 ± 标准差)和 10 ± 2 之间),但甲状腺血管及其周围组织(90 ± 17)和小脑(270 ± 18)除外。在此,比值朝着更高的 Gd 浓度显著增加。

结论

本研究结果表明,在体内各种组织中,La 的长期沉积以及另外发现的 Gd 的相似定位。考虑到碳酸镧的总给药量高达 11.5kg,La 的沉积相对较低,这表明 La 的吸收和/或排泄较高。然而,沉积的 La 总量是显著的,这引发了对可能的不良反应的关注。比值法允许使用额外生成的 Gd 数据,而无需详细了解可能的 GBCA 应用。大脑中 Gd-to-La-ratio 的显著降低可能是由于胃中释放的 La 离子被摄取,从而阻碍了血脑屏障的穿越,而静脉注射的 GBCA 可能在已经穿过血脑屏障时首先脱螯合。

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