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A dextran-based probe for the targeted magnetic resonance imaging of tumours expressing prostate-specific membrane antigen

Nature Biomedical Engineering volume 1, pages 977–982 (2017)Cite this article

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Abstract

Safe imaging agents that are able to render the expression and distribution of cancer receptors, enzymes or other biomarkers would facilitate clinical screening of the disease. Here, we show that diamagnetic dextran particles that are coordinated to a urea-based targeting ligand for prostate-specific membrane antigen (PSMA) enable targeted magnetic resonance imaging (MRI) of the PSMA receptor. In a xenograft model of prostate cancer, micromolar concentrations of the dextran–ligand probe provided sufficient signal to specifically detect PSMA-expressing tumours via chemical exchange saturation transfer MRI. The dextran-based probe could be detected via the contrast that originated from dextran hydroxyl protons, thereby avoiding the need of chemical substitution for radioactive or metallic labelling. Because dextrans are currently used clinically, dextran-based contrast agents may help to extend receptor-targeted imaging to clinical MRI.

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Acknowledgements

This work was supported by the US National Institutues of Health grants U54CA151838, R21EB015609, R03EB021573, R01CA134675, R01CA184228, R01CA211087, R21CA215860, U01CA183031, P41EB024495, R01EB019934 and R01EB015032.

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Author notes

  1. Guanshu Liu and Sangeeta Ray Banerjee contributed equally to this work.

Authors and Affiliations

  1. The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Guanshu Liu, Sangeeta Ray Banerjee, Nirbhay Yadav, Ala Lisok, Anna Jablonska, Jiadi Xu, Yuguo Li, Martin G. Pomper & Peter van Zijl

  2. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA

    Guanshu Liu, Nirbhay Yadav, Jiadi Xu, Yuguo Li & Peter van Zijl

  3. Department of Nuclear Medicine, Peking University First Hospital, Beijing, China

    Xing Yang

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  1. Guanshu Liu
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Contributions

G.L., S.R.B., M.G.P. and P.v.Z. conceived and designed the experiments. S.R.B. and X.Y. synthesized and characterized the agents. S.R.B. and A.L. prepared the animal model. G.L., Y.L. and N.Y. performed the MRI studies. A.J., S.R.B. and G.L. performed the immunohistochemistry. G.L. and P.v.Z. analysed the data. G.L. and P.v.Z. co-wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Guanshu Liu or Peter van Zijl.

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Liu, G., Banerjee, S.R., Yang, X. et al. A dextran-based probe for the targeted magnetic resonance imaging of tumours expressing prostate-specific membrane antigen. Nat Biomed Eng 1, 977–982 (2017). https://doi.org/10.1038/s41551-017-0168-8

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