Ashouri Hanieh, Riyahi Alam Nader, Khoobi Mehdi, Haghgoo Soheila, Rasouli Zahra, Gholami Mahdi
Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences(TUMS), Tehran, Iran.
Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences(TUMS), Tehran, Iran; Concordia University, Perform Center, Montreal, Quebec, Canada; Biomaterials Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.
Magn Reson Imaging. 2024 Apr;107:120-129. doi: 10.1016/j.mri.2024.01.003. Epub 2024 Jan 11.
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).
在肾功能受损（4级和5级）的患者中，磁共振成像（MRI）中使用传统的钆（Gd）基造影剂会带来显著的肾源性系统性纤维化（NSF）综合征风险。为解决这一问题，一项新研究引入了一种新型的涂有β-环糊精（βCD）的代谢性氧化钆纳米颗粒（Gd2O3 NPs）。该研究旨在通过使用磁共振分子成像量化肾功能受损大鼠组织中的钆沉积生物分布来研究NSF综合征。这是首次采用这种方法的研究。一组20只大鼠被分为四组，每组五只大鼠接受了5/6肾切除术。大鼠每周静脉注射两次，连续六周，分别注射剂量为0.1 mmol/kg的新型自制合成氧化钆聚环糊精（Gd2O3@PCD）、剂量为2.5 mmol/kg的常规造影剂（CAs）药物欧乃影（Gd-DTPA-BMA）和多它灵（Gd-DOTA），以及250 μl生理盐水。在注射前以及连续六周每周进行一次T1加权磁共振成像，以使用电感耦合等离子体质谱（ICP-MS）量化大鼠四个不同器官（皮肤、肝脏、心脏和肺）中的钆沉积。还计算了由于NSF诱导综合征导致的信噪比（SNR）与钆沉积生物分布之间的关系。研究结果表明，与其他组相比，Gd2O3@PCD组组织中的钆浓度显著更高，且无任何明显的组织病理学变化（P < 0.05）。在Gd2O3@PCD组中，钆主要沉积在皮肤，其次是肝脏、肺和心脏，皮肤没有增厚或硬化的症状。多它灵组皮肤、肝脏、肺和心脏中的钆浓度显著低于欧乃影组（P < 0.05）。在组织病理学检查中，欧乃影组显示真皮细胞增多。与多它灵组和欧乃影组相比，Gd2O3@PCD处理的大鼠在肝脏、心脏和肺中观察到明显的高强度信号。与传统的基于钆的CAs相比，新型代谢性Gd2O3@PCD具有更高的SNR、生物安全性以及更低的发生NSF概率，在临床磁共振分子成像（MRMI）中对诊断肾病患者具有潜在的适用性。
