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The Evolution of Iron Oxide Nanoparticles as MRI Contrast Agents

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Abstract

While the use of iron oxide nanoparticles as magnetic resonance contrast agents for clinical imaging is established, they are more recently experiencing renewed interest as alternatives to gadolinium-based contrast agents. Ultra-small iron oxide nanoparticles have unique pharmacokinetics, metabolic and imaging properties. These properties have led to improved techniques for imaging a variety of vascular, oncologic and inflammatory conditions with iron oxide nanoparticles. Current research efforts are aimed at harnessing the characteristics of these nanoparticles to advance magnetic resonance imaging techniques and explore new therapeutic potentials. While there are some limitations to the use of iron oxide nanoparticles, including allergies to parenteral iron and iron storage disorders, the practicable applications for these agents will continue to expand. The purpose of this review is to provide a brief overview of the history and synthesis of iron oxide nanoparticles, their current applications in clinical imaging and their prospective clinical applications.

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References

  1. R. Qiao, C. Yang, and M. Gao, J. Mater. Chem. 19 (35), 6274–6293 (2009). doi: 10.1039/b902394a.

    CAS  Google Scholar 

  2. Y.X.J. Wang, S. M. Hussain, and G.P. Krestin, Eur. Radiol. 11 (11), 2319–2331 (2001). doi: 10.1007/s003300100908.

    CAS  Google Scholar 

  3. C. Tassa, S.Y. Shaw, and R. Weissleder, Accounts of Chemical Research. 44 (10), 842–852 (2011). doi: 10.1021/ar200084x.

    CAS  Google Scholar 

  4. G. Acharya, A.K. Mitra, and K. Cholkar, in Emerging Nanotechnologies for Diagnostics, Drug Delivery and Medical Devices, edited by A.K. Mitra, K. Cholkar and A. Mandal (Elsevier Inc., New York, 2017), p. 217–248.

  5. M.W. Marashdeh, B. Ababneh, O.M. Lemine, A. Alsadig, K. Omri, L. El Mir, A. Sulieman, and E. Mattar, Results Phys. 15, 102651 (2019). doi: 10.1016/j.rinp.2019.102651.

    Google Scholar 

  6. D.D. Stark, R. Weissleder, G. Elizondo, P.F. Hahn, S. Saini, L.E. Todd, J. Wittenberg, and J.T. Ferrucci, Radiology. 168 (2), 297–301 (1988). doi: 10.1148/radiology.168.2.3393649.

    CAS  Google Scholar 

  7. Y.X.J. Wang, World J. Gastroenterol. 21 (47), 13400–13402 (2015). doi: 10.3748/wjg.v21.i47.13400.

    CAS  Google Scholar 

  8. K. Kallianos, T.S. Henry, Y. Yeghiazarians, J. Zimmet, K.A. Shunk, E.E. Tseng, V. Mahadevan, and M.D. Hope, Int. J. Cardiol. 231, P255–257 (2017). doi: 10.1016/j.ijcard.2016.12.147.

    Google Scholar 

  9. M.G. Harisinghani, M.A. Saksena, P.F. Hahn, B. King, J. Kim, M.T. Torabi and R. Weissleder, Am. J. Roentgenol. 186 (1), 144–148 (2006) doi: 10.2214/AJR.04.1287.

    Google Scholar 

  10. P.V. Pandharipande, J.T. Mora, R.N. Uppot, A. Goehler, M. Braschi, E.F. Halpern, G.S. Gazelle and M.G. Harisinghani, Am. J. Roentgenol. 193 (3), (2009). doi: 10.2214/AJR.08.2175.

    Google Scholar 

  11. S. Woo, C. H. Suh, S. Y. Kim, J. Y. Cho, and S. H. Kim, Am. J. Roentgenol. 210 (3), W95–W109 (2018). doi: 10.2214/AJR.17.18481.

    Google Scholar 

  12. J. Endrikat, S. Dohanish, N. Schleyer, S. Schwenke, S. Agarwal, and T. Balzer, Invest. Radiol. 53 (9), 541–550 (2018). doi: 10.1097/RLI.0000000000000462.

    Google Scholar 

  13. J. Ramalho, M. Ramalho, M. Jay, L. M. Burke, and R. C. Semelka, Magn. Reson. Imaging. 34 (10), 1394–1398 (2016). doi: 10.1016/j.mri.2016.09.005.

    CAS  Google Scholar 

  14. H.E. Daldrup-Link, Radiology. 284 (3) 616–629 (2017). doi: 10.1148/radiol.2017162759.

    Google Scholar 

  15. G.B. Toth, C.G. Varallyay, A. Horvath, et al.. Kidney International. 92 (1), 47–66 (2017). doi: 10.1016/j.kint.2016.12.037.

    CAS  Google Scholar 

  16. K.-L. Nguyen, T. Yoshida, F. Han, I. Ayad, B.L. Reemtsen, I.B. Salusky, G.M. Satou, P. Hu, J.P. Finn, J. Magn. Reson. Imaging. 45 (3), 804–812 (2017). doi: 10.1002/jmri.25412.

    Google Scholar 

  17. M.R. Bashir, L. Bhatti, D. Marin, and R.C. Nelson, Journal of Magnetic Resonance Imaging. 41 (4), 884–898 (2015). doi: 10.1002/jmri.24691.

    Google Scholar 

  18. H. Kordbacheh, V. Baliyan, A. Parakh, G. R. Wojtkiewicz, S. Hedgire, and M. G. Harisinghani, Abdominal Radiology. 44 (10), 3273–3284 (2019). doi: 10.1007/s00261-019-02163-4.

    Google Scholar 

  19. S. Stoumpos, M. Hennessy, A.T. Vesey, A. Radjenovic, R. Kasthuri, D.B. Kingsmore, P.B. Mark, G. Roditi, Eur. Radiol. 29 (7), 3543–3552 (2019). doi: 10.1007/s00330-019-06137-4.

    Google Scholar 

  20. K.-L. Nguyen, J.M. Moriarty, A.N. Plotnik, O. Aksoy, T. Yoshida, T.J. Shemin, W.M. Suh, J.P. Finn, Radiology. 286 (1), 326–337 (2018). doi: 10.1148/radiol.2017162899.

    Google Scholar 

  21. M.D. Hope, T.A. Hope, C. Zhu, F. Faraji, H. Haraldsson, K.G. Ordovas, and D. Saloner, Am. J. Roentgenol. 205 (3), W366–W373 (2015). doi: 10.2214/AJR.15.14534.

    Google Scholar 

  22. M.D. Hope, T.A. Hope, C. Zhu, F. Faraji, H. Haraldsson, K.G. Ordovas, and D. Saloner, Am. J. Roentgenol. 205 (3), W366–W373 (2015). doi: 10.2214/AJR.15.14534.

    Google Scholar 

  23. A.J. Degnan, A.J. Patterson, T.Y. Tang, S.P.S. Howarth, and J.H. Gillard, Cerebrovasc. Dis. 34 (2), 169–173 (2012). doi: 10.1159/000339984.

    Google Scholar 

  24. R. Newby, R. Forsythe, O. McBride, et al.., Circulation. 136 (9), 787–797 (2017). doi: 10.1161/CIRCULATIONAHA.117.028433.

    Google Scholar 

  25. J.P. Netto, J. Iliff, D. Stanimirovic, K.A. Krohn, B. Hamilton, C. Varallyay, S. Gahramanov, H. Daldrup-Link, C. d’Esterre, B. Zlokovic, H. Sair, Y. Lee, S. Taheri, R. Jain, A. Panigrahy, D.S. Reich, L.R. Drewes, M. Castillo, and E.A. Neuwelt, Neurosurgery. 82 (6), 770–780 (2018).

    Google Scholar 

  26. C.G. Varallyay, E. Nesbit, A. Horvath, P. Varallyay, R. Fu, S. Gahramanov, L.L. Muldoon, X. Li, W.D. Rooney, and E.A. Neuwelt, J. Magn. Reson. Imaging. 48 (2), 441–448 (2018). doi: 10.1002/jmri.25943.

    Google Scholar 

  27. S. Gahramanov, L.L. Muldoon, C.G. Varallyay, X. Li, D.F. Kraemer, R. Fu, B.E. Hamilton, W.D. Rooney, and E.A. Neuwelt, Radiology. 266 (3), 842–852 (2013). doi: 10.1148/radiol.12111472.

    Google Scholar 

  28. H.M. Sandler, R.L. Dunn, P.W. McLaughlin, J.A. Hayman, M.A. Sullivan, and J.M.G. Taylor, Int. J. Radiat. Oncol. Biol. Phys. 48 (3), 629–633 (2000). doi: 10.1016/S0360-3016(00)00717-3.

    CAS  Google Scholar 

  29. J. Hegarty, P.V Beirne, E. Walsh, H. Comber, T. Fitzgerald, and M. Wallace Kazer, Cochrane Database Syst. Rev. 11 (2010). doi: 10.1002/14651858.cd006590.pub2.

  30. A. O’Shea, A. Kilcoyne, S.S. Hedgire, and M.G. Harisinghani, Abdominal Radiology. 45, 2198–2212 (2020). doi: 10.1007/s00261-019-02285-9.

    Google Scholar 

  31. M.G. Harisinghani, S. Saini, R. Weissleder, P.F. Hahn, R.K. Yantiss, C. Tempany, B.J. Wood, and P.R. Mueller, Am. J. Roentgenol. 172 (5), 1347–1351 (1999). doi: 10.2214/ajr.172.5.10227514.

    CAS  Google Scholar 

  32. M.G. Harisinghani, J. Barentsz, P.F. Hahn, W.M. Deserno, S. Tabatabaei, C. Hulsbergen van de Kaa, J. de la Rosette, and R. Weissleder, N. Engl. J. Med. 348 (25), 2491–2499 (2003). doi: 10.1056/NEJMoa022749.

    Google Scholar 

  33. B. Turkbey, M. Czarniecki, J.H. Shih, S.A. Harmon, P.K. Agarwal, A.B. Apolo, D.E. Citrin, J.L. Gulley, M. Harisinghani, R.A. Madan, A.R. Metwalli, E. Paquette, P.A. Pinto, S. Rais-Bahrami, L.S. Rowe, B.J. Wood, P.M. Jacobs, L. Lindenberg, W. Dahut, and P.L. Choyke, Am. J. Roentgenol. 214 (1), 105–113 (2020). doi: 10.2214/AJR.19.21264.

    Google Scholar 

  34. D.L.J. Thorek, D. Ulmert, N.-F.M. Diop, M.E. Lupu, M.G. Doran, R. Huang, D.S. Abou, S.M. Larson, and J. Grimm, Nat. Commun. 5, 3097 (2014). doi: 10.1038/ncomms4097.

    Google Scholar 

  35. A.M. Muehe, F. Siedek, A.J. Theruvath, J. Seekins, S.L. Spunt, A. Pribnow, F.K. Hazard, T. Liang, and H. Daldrup-Link, Theranostics. 10 (8), 3612–3621 (2020). doi: 10.7150/thno.40606.

    CAS  Google Scholar 

  36. C. Pérez-Medina, J. Tang, D. Abdel-Atti, B. Hogstad, M. Merad, E.A. Fisher, Z.A. Fayad, J.S. Lewis, W.J.M. Mulder, and T. Reiner, J. Nucl. Med. 56 (8), 1272–1277 (2015). doi: 10.2967/jnumed.115.158956.

    Google Scholar 

  37. T.L. Whiteside, Oncogene. 27 (45), 5904–5912 (2008). doi: 10.1038/onc.2008.271.

    CAS  Google Scholar 

  38. R. Noy and J.W. Pollard, Immunity. 41 (1), 49–61 (2014). doi: 10.1016/j.immuni.2014.06.010.

    CAS  Google Scholar 

  39. J.M. Jaynes, R. Sable, M. Ronzetti, et al.., Sci. Transl. Med. 12, (530), (2020). doi: 10.1126/scitranslmed.aax6337.

    Google Scholar 

  40. R. Yang, S. Sarkar, V.W. Yong, and J.F. Dunn, Magn. Reson. Insights. 11, 1178623X1877197 (2018). doi: 10.1177/1178623×18771974.

    Google Scholar 

  41. M. Aghighi, A.J. Theruvath, A. Pareek, L.L. Pisani, R. Alford, A.M. Muehe, T.K. Sethi, S.J. Holdsworth, D.K. Hazard, D. Gratzinger, S. Luna-Fineman, R. Advani, S.L. Spunt, and H.E. Daldrup-Link, Clin. Cancer Res. 24 (17), 4110–4118 (2018). doi: 10.1158/1078-0432.CCR-18-0673.

    CAS  Google Scholar 

  42. R.K. Ramanathan, R.L. Korn, N. Raghunand, J.C. Sachdev, R.G. Newbold, G. Jameson, G.J. Fetterly, J. Prey, S.G. Klinz, J. Kim, J. Cain, B.S. Hendriks, D.C. Drummond, E. Bayever, and J.B. Fitzgerald, Clin. Cancer Res. 23 (14), 3638–3648 (2017). doi: 10.1158/1078-0432.CCR-16-1990.

    CAS  Google Scholar 

  43. M.P. Moy, J. Sauk, and M.S. Gee, Gastroenterol. Res. Pract. 2016, (2016). doi: 10.1155/2016/8168695.

  44. J.L. Gaglia, A.R. Guimaraes, M. Harisinghani, S.E. Turvey, R. Jackson, C. Benoist, D. Mathis, and R. Weissleder, J. Clin. Invest. 121 (1), 442–445 (2011). doi: 10.1172/JCI44339.

    CAS  Google Scholar 

  45. J.L. Gaglia, M. Harisinghani, I. Aganj, G.R. Wojtkiewicz, S. Hedgire, C. Benoist, D. Mathis, and R. Weissleder, Proc. Natl. Acad. Sci. U. S. A. 112 (7), 2139–2144 (2015). doi: 10.1073/pnas.1424993112.

    CAS  Google Scholar 

  46. R.T. Castaneda, A. Khurana, R. Khan, and H.E. Daldrup-Link, J. Vis. Exp. 57 (2011). doi: 10.3791/3482.

  47. L. Liu and C. Ho, Curr. Protoc. Stem Cell Biol. 43 (1), 2B.7.1–2B.7.14 (2017). doi: 10.1002/cpsc.38.

    Google Scholar 

  48. K. Li, H. Nejadnik, and H.E. Daldrup-Link, Drug Discovery Today. 22 (9), 1421–1429 (2017). doi: 10.1016/j.drudis.2017.04.008.

    CAS  Google Scholar 

  49. M.A. Miller, S. Gadde, C. Pfirschke, C. Engblom, M.M. Sprachman, R.H. Kohler, K.S. Yang, A.M. Laughney, G. Wojtkiewicz, N. Kamaly, S. Bhonagiri, M.J. Pittet, O.C. Farokhzad, and R. Weissleder, Sci. Transl. Med. 7 (314), 314ra183 (2015). doi: 10.1126/scitranslmed.aac6522.

    Google Scholar 

  50. C. Wang, D.J. Graham, R.C. Kane, D. Xie, M. Wernecke, M. Levenson, T.E. MaCurdy, M. Houstoun, Q. Ryan, S. Wong, K. Mott, T.-C. Sheu, S. Limb, C. Worrall, J.A. Kelman, and M.E. Reichman, JAMA - J. Am. Med. Assoc. 314 (19), 2062–2068 (2015). doi: 10.1001/jama.2015.15572.

    CAS  Google Scholar 

  51. C.G. Varallyay, G.B. Toth, R. Fu, J.P. Netto, J. Firkins, P. Ambady, and E.A. Neuwelt, Am. J. Neuroradiol. 38 (7), 1297–1302 (2017). doi: 10.3174/ajnr.A5188.

    CAS  Google Scholar 

  52. G. Rostoker and N.D. Vaziri, Heliyon. 5 (7), e02045 (2019). doi: 10.1016/j.heliyon.2019.e02045.

    Google Scholar 

  53. J. Albaramki, E.M. Hodson, J.C. Craig, and A.C. Webster, Cochrane Database Syst. Rev. 1 (2012). doi: 10.1002/14651858.cd007857.pub2.

  54. G. Rostoker, M. Griuncelli, C. Loridon, T. Magna, P. Janklewicz, G. Drahi, H. Dahan, and Y. Cohen, PLoS One. 9 (12), (2014). doi: 10.1371/journal.pone.0115096.

    Google Scholar 

  55. P. Storey, R.P. Lim, H. Chandarana, A.B. Rosenkrantz, D. Kim, D.R. Stoffel, and V.S. Lee, Invest. Radiol. 47 (12), 717–724 (2012). doi: 10.1097/RLI.0b013e31826dc151.

    CAS  Google Scholar 

  56. G. Rostoker and Y. Cohen, J. Comput. Assist. Tomogr. 38, (6), 843–844 (2014). doi: 10.1097/RCT.0000000000000146.

    Google Scholar 

  57. Feraheme Radiologist Letter. AMAG Pharmaceuticals. http://www.feraheme.com/pdfs/Feraheme-Radiologist-Letter.pdf (accessed May 30, 2020).

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Authors and Affiliations

  1. Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA

    Aileen O’Shea (MB BCh BAO), Anushri Parakh (MBBS MD), Rita Maria Lahoud (MD), Sandeep Hedgire (MD) & Mukesh G. Harisinghani (MD)

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  1. Aileen O’Shea
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O’Shea, A., Parakh, A., Lahoud, R.M. et al. The Evolution of Iron Oxide Nanoparticles as MRI Contrast Agents. MRS Advances 5, 2157–2168 (2020). https://doi.org/10.1557/adv.2020.311

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