Lu Yang, Xu Yun-Jun, Zhang Guo-Bing, Ling Daishun, Wang Ming-Quan, Zhou Yong, Wu Ya-Dong, Wu Tao, Hackett Michael J, Hyo Kim Byung, Chang Hogeun, Kim Jonghoon, Hu Xin-Tian, Dong Liang, Lee Nohyun, Li Fangyuan, He Jia-Cai, Zhang Li, Wen Hui-Qin, Yang Bo, Hong Choi Seung, Hyeon Taeghwan, Zou Duo-Hong
Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, 08826, Republic of Korea.
School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul, 08826, Republic of Korea.
Nat Biomed Eng. 2017 Aug;1(8):637-643. doi: 10.1038/s41551-017-0116-7. Epub 2017 Jul 31.
Iron-oxide-based contrast agents for magnetic resonance imaging (MRI) had been clinically approved in the United States and Europe, yet most of these nanoparticle products were discontinued owing to failures to meet rigorous clinical requirements. Significant advances have been made in the synthesis of magnetic nanoparticles and their biomedical applications, but several major challenges remain for their clinical translation, in particular large-scale and reproducible synthesis, systematic toxicity assessment, and their preclinical evaluation in MRI of large animals. Here, we report the results of a toxicity study of iron oxide nanoclusters of uniform size in large animal models, including beagle dogs and the more clinically relevant macaques. We also show that iron oxide nanoclusters can be used as T MRI contrast agents for high-resolution magnetic resonance angiography in beagle dogs and macaques, and that dynamic MRI enables the detection of cerebral ischaemia in these large animals. Iron oxide nanoclusters show clinical potential as next-generation MRI contrast agents.
用于磁共振成像（MRI）的基于氧化铁的造影剂已在美国和欧洲获得临床批准，但由于未能满足严格的临床要求，这些纳米颗粒产品大多已停产。磁性纳米颗粒的合成及其生物医学应用取得了重大进展，但其临床转化仍面临几个主要挑战，特别是大规模且可重复的合成、系统毒性评估以及在大型动物MRI中的临床前评估。在此，我们报告了在包括比格犬和更具临床相关性的猕猴在内的大型动物模型中对均匀尺寸的氧化铁纳米团簇进行毒性研究的结果。我们还表明，氧化铁纳米团簇可用作比格犬和猕猴高分辨率磁共振血管造影的T MRI造影剂，并且动态MRI能够检测这些大型动物的脑缺血。氧化铁纳米团簇作为下一代MRI造影剂显示出临床潜力。
