Journal of Trace Elements in Medicine and Biology ( IF 3.6 ) Pub Date : 2020-10-24 , DOI: 10.1016/j.jtemb.2020.126665 Patrick Bücker 1 , Henning Richter 2 , Alexander Radbruch 3 , Michael Sperling 4 , Marcus Brand 5 , Markus Holling 6 , Veerle Van Marck 7 , Werner Paulus 8 , Astrid Jeibmann 8 , Uwe Karst 1
|
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 La3+ 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.
中文翻译：
医源性镧和钆在人体内的沉积模式取决于传递的化学结合形式
背景
最近，据报道来自线性 GBCA 的钆沉积在身体的各个部位。除了钆，其他镧系元素也用于医疗。在目前的研究中，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的患者的镧沉积，并将其与额外发现的 Gd 沉积进行了比较。
方法
研究了长期应用碳酸镧以及可能应用 GBCA 的两名患者的组织标本。钆和镧的空间分布通过组织切片的定量激光烧蚀-电感耦合等离子体质谱 (LA-ICP-MS) 成像来确定。比较了不同器官中钆和镧的沉积，并在图像内的单个像素基础上研究了 Gd 浓度与 La 浓度的比率（Gd 与 La 的比率）。
结果
在两名患者的所有研究组织中都发现了 Gd 和 La 的沉积。Gd 和 La 对所有样品都表现出高度的空间相关性，主要沉积位于血管的中层（中膜）。除了甲状腺脉管系统和周围组织 (90 ± 17) 以及小脑（ 270±18）。在这里，该比率朝着更高的 Gd 浓度显着增加。
结论
这项研究的结果证明了 La 的长期沉积和另外发现的 Gd 在身体各种组织中的类似定位。La 沉积相对较低，考虑到碳酸镧的总给药量高达 11.5 kg，表明镧的低吸收和/或高排泄。然而，沉积的 La 总量很大，并引发了关于可能的不良副作用的问题。比率方法允许使用额外生成的 Gd 数据，而无需详细了解可能的 GBCA 应用程序。大脑中 Gd 与 La 比率的显着降低可能是因为镧被释放并被吸收为游离的 La 3+ 胃中的离子会阻碍血脑屏障的穿过，而静脉注射的 GBCAs 可能会在它们已经穿过血脑屏障时首先脱钩。
京公网安备 11010802027423号