Applied Magnetic Resonance

, Volume 46, Issue 3, pp 349–355 | Cite as

Gadolinium-Loaded Viral Capsids as Magnetic Resonance Imaging Contrast Agents

  • Robert J. Usselman
  • Shefah Qazi
  • Priyanka Aggarwal
  • Sandra S. Eaton
  • Gareth R. Eaton
  • Stephen Russek
  • Trevor Douglas


Polymeric nanohybrid P22 virus capsids were used as templates for high density Gd3+ loading to explore magnetic field-dependent (0.5–7.0 T) proton relaxivity. The field-dependence of relaxivity by the spatially constrained Gd3+ in the capsids was similar when either the loading of the capsids or the concentration of capsids was varied. The ionic longitudinal relaxivity, r 1, decreased from 25–32 mM−1 s−1 at 0.5 T to 6–10 mM−1 s−1 at 7 T. The ionic transverse relaxivity, r 2, increased from 28–37 mM−1 s−1 at 0.5 T to 39–50 mM−1 s−1 at 7 T. The r 2/r 1 ratio increased linearly with increasing magnetic field from about 1 at 0.5 T, which is typical of T 1 contrast agents, to 5–8 at 7 T, which is approaching the ratios for T 2 contrast agents. Increases in electron paramagnetic resonance line widths at 80 and 150 K and higher microwave powers required for signal saturation indicate enhanced Gd3+ electron spin relaxation rates for the Gd3+-loaded capsids than for low concentration Gd3+. The largest r 2/r 1 at 7 T was for the highest cage loading, which suggests that Gd3+–Gd3+ interactions within the capsid enhance r 2 more than r 1.


Electron Paramagnetic Resonance ATRP DTPA High Magnetic Field Magnetic Resonance Imaging Contrast Agent 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by an award from the American Heart Association (SQ) and was supported in part by a grant from the National Institutes of Health, NIBIB R01-EB012027 and by internal funding at the University of Denver. This work was partially supported by the US government, not protected by US copyright.

Supplementary material

723_2014_639_MOESM1_ESM.docx (794 kb)
Supplementary material 1 (DOCX 793 kb)


  1. 1.
    E. Toth, L. Helm, A.E. Merbach, Top. Current Chem. 221, 61–101 (2002)CrossRefGoogle Scholar
  2. 2.
    P. Caravan, C.T. Farrar, L. Frullano, R. Uppal, Contrast Media Mol. Imaging 4, 89–100 (2009)CrossRefGoogle Scholar
  3. 3.
    V.C. Pierce, M.J. Allen, P. Caravan, J. Biol. Inorg. Chem. 19, 127–131 (2014)CrossRefGoogle Scholar
  4. 4.
    L. Helm, Future. Med. Chem. 2, 385–396 (2010)Google Scholar
  5. 5.
    L. Helm, Chimia 65, 696–698 (2011)CrossRefGoogle Scholar
  6. 6.
    P. Caravan, J.J. Ellison, T.J. McMurry, R.B. Lauffer, Chem. Rev. 99(9), 2293–2352 (1999)CrossRefGoogle Scholar
  7. 7.
    L. Ciobanu, O. Reynaud, L. Uhrig, B. Jarraya, D. Le Bihan, PLoS ONE 7(3), e32645 (2012)CrossRefADSGoogle Scholar
  8. 8.
    L. Uhrig, L. Ciobanu, B. Djemai, D. Le Bihan, B. Jarraya, PLoS ONE 9(7), e100323 (2014)CrossRefADSGoogle Scholar
  9. 9.
    R.B. Lauffer, Chem. Rev. 87(5), 901–927 (1987)CrossRefGoogle Scholar
  10. 10.
    M. Botta, L. Tei, Eur. J. Inorg. Chem. 2012(12), 1945–1960 (2012)CrossRefGoogle Scholar
  11. 11.
    S.H. Koenig, K.E. Kellar, Magn. Reson. Med. 34(2), 227–233 (1995)CrossRefGoogle Scholar
  12. 12.
    P.J. Klemm, W.C. Floyd, C.M. Andolina, J.M.J. Frechet, K.N. Raymond, Eur. J. Inorg. Chem. 2012(12), 2108–2114 (2012)CrossRefGoogle Scholar
  13. 13.
    G.L. Davies, I. Kramberger, J.J. Davis, Chem. Commun. 49(84), 9704–9721 (2013)CrossRefGoogle Scholar
  14. 14.
    L. Liepold, S. Anderson, D. Willits, L. Oltrogge, J.A. Frank, T. Douglas, M. Young, Magn. Reson. Med. 58(5), 871–879 (2007)CrossRefGoogle Scholar
  15. 15.
    J. Lucon, S. Qazi, M. Uchida, G.J. Bedwell, B. LaFrance, P.E. Prevelige, T. Douglas, Nat. Chem. 4(10), 781–788 (2012)CrossRefGoogle Scholar
  16. 16.
    S. Qazi, L.O. Liepold, M.J. Abedin, B. Johnson, P. Prevelige, J.A. Frank, T. Douglas, Mol. Pharm. 10(1), 11–17 (2013)CrossRefGoogle Scholar
  17. 17.
    S. Qazi, M. Uchida, R.J. Usselman, R. Shearer, E. Edwards, T. Douglas, J. Biol. Inorg. Chem. 19(2), 237–246 (2014)CrossRefGoogle Scholar
  18. 18.
    R.J. Usselman, E.D. Walter, D. Willits, T. Douglas, M. Young, D.J. Singel, J. Am. Chem. Soc. 133(12), 4156–4159 (2011)CrossRefGoogle Scholar
  19. 19.
    A. Datta, J.M. Hooker, M. Botta, M.B. Francis, S. Aime, K.N. Raymond, J. Am. Chem. Soc. 130(8), 2546–2552 (2008)CrossRefGoogle Scholar
  20. 20.
    J. Min, H. Jung, H.H. Shin, G. Cho, H. Cho, S. Kang, Biomacromolecules 14(7), 2332–2339 (2013)CrossRefGoogle Scholar
  21. 21.
    K.J. Chen, S.M. Wolahan, H. Wang, C.H. Hsu, H.W. Chang, A. Durazo, L.P. Hwang, M.A. Garcia, Z.K. Jiang, L. Wu, Y.Y. Lin, H.R. Tseng, Biomaterials 32(8), 2160–2165 (2011)CrossRefGoogle Scholar
  22. 22.
    S.H. Koenig, Magn. Reson. Med. 22(2), 183–190 (1991)CrossRefGoogle Scholar
  23. 23.
    M. Gueron, J. Magn. Reson. 19, 58–66 (1975)ADSGoogle Scholar
  24. 24.
    Q.L. Vuong, S. Van Doorslaer, J.L. Bridot, C. Argante, G. Alejandro, R. Hermann, S. Disch, C. Mattea, S. Stapf, Y. Gossuin, MAGMA 25(6), 467–478 (2012)CrossRefGoogle Scholar
  25. 25.
    G.M. Nicolle, L. Helm, A.E. Merbach, Magn. Reson. Chem. 41, 794–799 (2003)CrossRefGoogle Scholar
  26. 26.
    P. Gong, Z.Y. Chen, Y.Y. Chen, W. Wang, X.S. Wang, A.G. Hu, Chem. Commun. 47(14), 4240–4242 (2011)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Robert J. Usselman
    • 1
  • Shefah Qazi
    • 2
  • Priyanka Aggarwal
    • 3
  • Sandra S. Eaton
    • 3
  • Gareth R. Eaton
    • 3
  • Stephen Russek
    • 1
  • Trevor Douglas
    • 4
  1. 1.Electromagnetics DivisionNational Institute of Standards and TechnologyBoulderUSA
  2. 2.Department of Chemistry and BiochemistryMontana State UniversityBozemanUSA
  3. 3.Department of Chemistry and BiochemistryUniversity of DenverDenverUSA
  4. 4.Department of ChemistryIndiana UniversityBloomingtonUSA

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