在磁共振成像(MRI)中使用基于常规钆(Gd)的造影剂会对肾功能受损(4级和5级)的患者造成肾源性系统性纤维化(NSF)综合征的重大风险。为了解决这个问题,一项新的研究引入了一种新型的代谢氧化钆纳米颗粒(Gd2O3NPs)包覆β-环糊精(βCD)。本研究旨在通过MR分子成像定量肾损害大鼠组织Gd沉积生物分布来研究NSF综合征。这是第一个使用这种方法的研究。20只大鼠分为四组,每只包含5只接受5/6肾切除术的大鼠。大鼠以0.1mmol/kg的剂量接受了12次静脉注射新型的自制合成氧化钆聚环糊精(Gd2O3@PCD),Omniscan(Gd-DTPA-BMA)和Dotarem(Gd-DOTA)的常规造影剂(CA)药物,剂量为2.5mmol/kg,和250μl盐水在六周内每周两次注射。在注射前进行T1加权MR成像,每周一次,持续六周,以量化四个不同器官中的Gd沉积(皮肤,肝脏,心,和肺)在大鼠中使用电感耦合等离子体质谱法(ICP-MS)。还计算了信噪比(SNR)与NSF引起的Gd沉积生物分布之间的关系。研究结果表明,Gd2O3@PCD组组织中Gd浓度明显高于其他组,无明显组织病理学改变(P<0.05)。在Gd2O3@PCD组中,Gd主要沉积在皮肤上,其次是肝脏,肺,和心,没有任何皮肤增厚或硬化的症状。皮肤中的Gd浓度,肝脏,肺,Dotarem组的心脏明显低于Omniscan组(P<0.05)。在组织病理学检查中,Omniscan组显示真皮细胞增加。与Dotarem和Omniscan组相比,在Gd2O3@PCD处理的大鼠中观察到明显的高强度,心,还有肺.与传统的基于Gd的CA相比,具有增加的信噪比的新型代谢Gd2O3@PCD,生物安全,发展NSF的可能性要低得多,在临床MR分子成像(MRMI)中诊断肾脏疾病具有潜在的适用性。
The use of conventional gadolinium(Gd)-based contrast agents in magnetic resonance imaging (MRI) poses a significant risk of Nephrogenic Systemic Fibrosis (
NSF) syndrome in patients with impaired renal function (grades 4 and 5). To address this issue, a new study has introduced a novel metabolic Gadolinium oxide nanoparticle (Gd2O3 NPs) coated with β-cyclodextrin (βCD). The study aims to investigate
NSF syndrome by quantifying tissue Gd deposition biodistribution in renal impairment rats using MR molecular imaging. This is the first study of its kind to use this approach. A group of 20 rats were divided into four groups, each containing five rats that underwent 5/6 nephrectomy. The rats received 12 intravenous injections of a novel homemade synthesized gadolinium oxide polycyclodextrin (Gd2O3@PCD) at a dose of 0.1 mmol/kg, conventional contrast agents (CAs) drugs of Omniscan (Gd-DTPA-BMA) and Dotarem (Gd-DOTA), at a dose of 2.5 mmol/kg, and 250 μl saline for two injections per week during six weeks. T1-weighted MR imaging was performed before the injections and once a week for six weeks to quantify Gd deposition in four different organs (skin, liver, heart, and lung) in rats using inductively coupled plasma mass spectrometry (ICP-MS). The relationship between Signal-to-Noise Ratio (SNR) and biodistribution of Gd deposition due to
NSF-induced syndrome was also calculated. The results of the study showed that the Gd concentrations in tissues were significantly higher in the Gd2O3@PCD group compared to the other groups, without any significant histopathological changes (P < 0.05). In the Gd2O3@PCD group, Gd was mainly deposited in the skin, followed by the liver, lung, and heart, without any symptoms of thickening or hardening of the skin. The Gd concentrations in the skin, liver, lung, and heart were significantly lower in the Dotarem group than in the Omniscan group (P < 0.05). In the histopathological examinations, the Omniscan group showed increased cellularity in the dermis. A significant hyperintensity was observed in the Gd2O3@PCD-treated rats compared to the Dotarem and Omniscan groups in the liver, heart, and lung. Compared to conventional Gd-based CAs, the novel metabolically Gd2O3@PCD with increased SNR, biosafety, and a considerably lower probability of developing
NSF, has potential applicability for diagnosing patients with renal diseases in clinical MR Molecular Imaging (MRMI).