Kanakia Shruti, Toussaint Jimmy, Hoang Dung Minh, Mullick Chowdhury Sayan, Lee Stephen, Shroyer Kenneth R, Moore William, Wadghiri Youssef Z, Sitharaman Balaji
Department of Biomedical Engineering, Stony Brook University, New York, NY USA.
Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, New York, NY USA.
Sci Rep. 2015 Dec 2;5:17182. doi: 10.1038/srep17182.
Current clinical Gd(3+)-based T1 magnetic resonance imaging (MRI) contrast agents (CAs) are suboptimal or unsuitable, especially at higher magnetic fields (>1.5 Tesla) for advanced MRI applications such as blood pool, cellular and molecular imaging. Herein, towards the goal of developing a safe and more efficacious high field T1 MRI CA for these applications, we report the sub-acute toxicity and contrast enhancing capabilities of a novel nanoparticle MRI CA comprising of manganese (Mn(2+)) intercalated graphene nanoparticles functionalized with dextran (hereafter, Mangradex) in rodents. Sub-acute toxicology performed on rats intravenously injected with Mangradex at 1, 50 or 100 mg/kg dosages 3 times per week for three weeks indicated that dosages ≤50 mg/kg could serve as potential diagnostic doses. Whole body 7 Tesla MRI performed on mice injected with Mangradex at a potential diagnostic dose (25 mg/kg or 455 nanomoles Mn(2+)/kg; ~2 orders of magnitude lower than the paramagnetic ion concentration in a typical clinical dose) showed persistent (up to at least 2 hours) contrast enhancement in the vascular branches (Mn(2+) concentration in blood at steady state = 300 ppb, per voxel = 45 femtomoles). The results lay the foundations for further development of Mangradex as a vascular and cellular/ molecular MRI probe.
目前基于钆（Gd(3+)）的临床T1磁共振成像（MRI）造影剂（CAs）并不理想或不合适，尤其是在更高磁场（>1.5特斯拉）下，无法用于诸如血池、细胞和分子成像等先进的MRI应用。在此，为了开发一种用于这些应用的安全且更有效的高场T1 MRI造影剂，我们报告了一种新型纳米颗粒MRI造影剂在啮齿动物中的亚急性毒性和造影增强能力，该造影剂由用葡聚糖功能化的锰（Mn(2+)）插层石墨烯纳米颗粒组成（以下简称Mangradex）。对大鼠进行的亚急性毒理学实验表明，每周静脉注射3次Mangradex，剂量分别为1、50或100 mg/kg，持续三周，结果显示剂量≤50 mg/kg可作为潜在的诊断剂量。对注射了潜在诊断剂量（25 mg/kg或455纳摩尔Mn(2+)/kg；比典型临床剂量中的顺磁性离子浓度低约2个数量级）的Mangradex的小鼠进行全身7特斯拉MRI检查，结果显示血管分支中存在持续（至少持续2小时）的造影增强（稳态下血液中的Mn(2+)浓度 = 300 ppb，每体素 = 45飞摩尔）。这些结果为进一步将Mangradex开发成血管和细胞/分子MRI探针奠定了基础。
