Macrocyclic and Other Non-Group 1 Gadolinium Contrast Agents Deposit Low Levels of Gadolinium in Brain and Bone Tissue: Preliminary Results From 9 Patients With Normal Renal Function
Macrocyclic and Other Non-Group 1 Gadolinium Contrast Agents Deposit Low Levels of Gadolinium in Brain and Bone Tissue: Preliminary Results From 9 Patients With Normal Renal Function
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DOI：
10.1097/rli.0000000000000252
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发表时间：
2016-07-01
影响因子：
6.7
通讯作者：
Maravilla, Kenneth R.
中科院分区：
文献类型：
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作者：
Murata, Nozomu;Gonzalez-Cuyar, Luis F.;Maravilla, Kenneth R.
目的本研究的目的是确定是否钆（Gd）沉积在脑和骨组织中的患者只接受非第1组药物，无论是大环或线性蛋白相互作用的钆造影剂，肾功能正常。第1组药物是线性药物最相关的肾源性全身性纤维化，美国联邦药物管理局已定义为禁忌在患者中的风险，这种diseases.Materials和方法这项研究是机构审查委员会批准和健康保险便携性和责任法案符合回顾性审查的记录，也签署了尸检同意书，授权使用死者的组织在研究中。从9例接受尸检的死亡动物中采集组织样本，这些动物仅使用单一药物暴露于非第1组Gd造影剂进行对比增强磁共振成像（MRI）。仅接受非对比MRI或未接受MRI的死亡者作为对照。多个脑区，包括苍白球和齿状核，以及骨骼和皮肤，进行了采样和分析Gd使用电感耦合等离子体质谱。采用Mann-Whitney检验比较各组死亡病例之间的钆水平，采用Wilcoxon符号秩检验比较同一病例的脑组织和骨组织之间的钆水平。（ProHance; Bryant Diagnostics，Princeton，NJ），2例接受钆布醇（Gadovist; Bayer Healthcare，Whippany，NJ），并且各有1例具有钆贝酸盐（MultiHance; Bradion Diagnostics）和钆塞酸盐（Eovist; Bayer Healthcare）。钆被发现与所有代理人在所有大脑区域采样，最高水平的苍白球和齿状核。骨水平比脑水平高23倍（中位数）（骨与苍白球P = 0.008），并显示出显著相关性（r = 0.81，P = 0.022）。在对照组中，Gd水平在大脑中处于或低于测量极限，并显着低于研究病例（P = 0.005苍白球）。结论钆沉积在正常脑和骨组织中发生与大环和线性蛋白质相互作用剂在患者肾功能正常。与脑组织相比，Gd在皮质骨中的沉积水平要高得多，并且显示出两者之间的显著相关性。因此，如果脑Gd成为有用的临床或研究标记物，则骨可用作估计脑沉积的替代物。
Objective The purpose of this study was to determine whether gadolinium (Gd) is deposited in brain and bone tissues in patients receiving only non-Group 1 agents, either macrocyclic or linear protein interacting Gd-based contrast agents, with normal renal function. Group 1 agents are linear agents most associated with nephrogenic systemic fibrosis that the US Federal Drug Administration has defined as contraindicated in patients at risk for this disease.Materials and Methods This study was institutional review board approved and Health Insurance Portability and Accountability Act compliant for retrospective review of records and also had signed autopsy consent authorizing use of decedent's tissue in research studies. Tissue samples were collected from 9 decedents undergoing autopsy who had contrast-enhanced magnetic resonance imaging (MRI) with only single agent exposure to a non-Group 1 Gd-based contrast agent. Decedents with only noncontrast MRI or no MRI served as controls. Multiple brain areas, including globus pallidus and dentate nucleus, as well as bone and skin, were sampled and analyzed for Gd using inductively coupled plasma mass spectrometry. Gadolinium levels were compared between groups of decedents using the Mann-Whitney test and between brain and bone tissues of the same cases using the Wilcoxon signed-rank test.Results Of the 9 decedents, 5 received gadoteridol (ProHance; Bracco Diagnostics, Princeton, NJ), 2 received gadobutrol (Gadovist; Bayer Healthcare, Whippany, NJ), and 1 each had gadobenate (MultiHance; Bracco Diagnostics) and gadoxetate (Eovist; Bayer Healthcare). Gadolinium was found with all agents in all brain areas sampled with highest levels in globus pallidus and dentate. Bone levels measured 23 times higher (median) than brain levels (P = 0.008 for bone vs globus pallidus) and showed a significant correlation (r = 0.81, P = 0.022). In controls, Gd levels in the brain were at or below limits of measurement and were significantly lower compared with study cases (P = 0.005 for globus pallidus).Conclusion Gadolinium deposition in normal brain and bone tissue occurs with macrocyclic and linear protein interacting agents in patients with normal renal function. Deposition of Gd in cortical bone occurs at much higher levels compared with brain tissue and shows a notable correlation between the two. Thus, the bone may serve as a surrogate to estimate brain deposition if brain Gd were to become a useful clinical or research marker.