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 ₁ 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）的基于铁氧化物的造影剂已在美国和欧洲得到临床批准，但由于未能满足严格的临床要求，因此大多数此类纳米颗粒产品都已停产。磁性纳米粒子的合成及其生物医学应用取得了重大进展，但是其临床翻译仍面临若干主要挑战，特别是大规模和可重现的合成，系统毒性评估以及它们在大型动物MRI中的临床前评估。在这里，我们报告了在大型动物模型（包括比格犬和更具临床意义的猕猴）中均匀大小的氧化铁纳米簇的毒性研究结果。我们还表明，氧化铁纳米团簇可以用作T ₁MRI造影剂可用于比格犬和猕猴的高分辨率磁共振血管造影，而动态MRI可检测这些大型动物的脑缺血。氧化铁纳米簇显示出作为下一代MRI造影剂的临床潜力。