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Iron oxide nanoclusters for T 1 magnetic resonance imaging of non-human primates


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.

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Fig. 1: Characterization and biocompatibility evaluation of the PEG–IONCs.
Fig. 2: MRA of a beagle dog and a macaque using PEG–IONCs.
Fig. 3: Dynamic susceptibility contrast perfusion-weighted imaging using PEG–IONCs in a beagle dog with cerebral ischaemia.
Fig. 4: Left cerebral ischaemia in a macaque.


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T.H. and S.H.C. acknowledge financial support from the Research Center Program of the Institute for Basic Science (IBS-R006-D1) in Korea. Y.L., D.-H.Z., D.L. and L.Z. acknowledge financial support from the National Key Research and Development Program of China (2016YFA0203600), National Natural Science Foundation of China (51572067, 21501039, 51503180, 31370983, 81401518, 31430028 and 5161101036), Fundamental Research Funds for the Central Universities (2015HGCH0009), Anhui Province Funds for Distinguished Young Scientists (1508085J08), Natural Science Foundation of Anhui Province (1708085ME114) and Young Top-Notch Talent Support Scheme at Anhui Medical University.

Author information




T.H., S.H.C., D.-H.Z., Y.L., D.L., Y.-J.X. and G.-b.Z. conceived the idea and designed the experiments. T.H., S.H.C. and D.-H.Z. supervised the research. Y.L., D.L., B.H.K., H.C., J.K. and N.L. processed the samples. D.-H.Z., T.W., Y.Z., J.-C.H. and L.Z. worked on the macaque breeding. G.-b.Z. and M.-q.W. worked on the cerebral ischaemia model. Y.-J.X., Y.L., D.L., N.L. and S.H.C. investigated the MR performance. T.W., Y.Z., L.Z. and H.-Q.W. processed the biocompatibility evaluation. Y.-D.W., L.D., F.L. and B.Y. performed the biodistribution and pharmacokinetic study in vivo. X.-T.H. performed the pathological analysis. Y.L., D.L., M.J.H., Y.-J.X., G.-b.Z., N.L., T.H., S.H.C. and D.-H.Z. wrote the paper. All authors analysed and discussed the results.

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Correspondence to Seung Hong Choi or Taeghwan Hyeon or Duo-Hong Zou.

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Lu, Y., Xu, YJ., Zhang, Gb. et al. Iron oxide nanoclusters for T 1 magnetic resonance imaging of non-human primates. Nat Biomed Eng 1, 637–643 (2017).

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