Applied Magnetic Resonance

, Volume 43, Issue 1–2, pp 223–236 | Cite as

Development of Dissolution DNP-MR Substrates for Metabolic Research

  • Magnus Karlsson
  • Pernille R. Jensen
  • Jens Ø. Duus
  • Sebastian Meier
  • Mathilde H. LercheEmail author


Dissolution dynamic nuclear polarization (DNP) provides a broadly applicable and rather simple means of developing probes for the real-time molecular imaging of cellular functions in vivo. The development of novel dissolution DNP substrate formulations is only rewarding for substrates that yield detectable metabolism within few minutes. In addition, in vivo preparations usually require amorphous samples at molar substrate concentrations for an efficient and reproducible DNP step with sufficient material. The composition ranges of novel substrate preparations need to be established experimentally owing to the solute’s impact on vitrification behavior. Here, we describe simple rationales employed in the development of novel substrate preparations for dissolution DNP-magnetic resonance. Solution state substrate polarizations between 10 and 40 % have been obtained for ~40 metabolic substrates in highly concentrated preparations that yield physiologically tolerable solutions with sufficient T 1 for in vivo nuclear magnetic resonance. Substrate metabolism is observed for novel in vivo substrates such as 3-hydroxybutyrate and aspartate.


Fumaric Acid Dynamic Nuclear Polarization Substrate Preparation Nuclear Magnetic Resonance Tube Cesium Salt 
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.


  1. 1.
    R.G. Griffin, T.F. Prisner, Phys. Chem. Chem. Phys. 12(22), 5737–5740 (2010)CrossRefGoogle Scholar
  2. 2.
    K. Golman, R.I. Zandt, M. Lerche, R. Pehrson, J.H. Ardenkjaer-Larsen, Cancer Res. 66(22), 10855–10860 (2006)CrossRefGoogle Scholar
  3. 3.
    P.R. Jensen, M. Karlsson, S. Meier, J.O. Duus, M.H. Lerche, Chemistry 15(39), 10010–10012 (2009)CrossRefGoogle Scholar
  4. 4.
    F.A. Gallagher, M.I. Kettunen, S.E. Day, D.E. Hu, J.H. Ardenkjaer-Larsen, R. Zandt, P.R. Jensen, M. Karlsson, K. Golman, M.H. Lerche, K.M. Brindle, Nature 453(7197), 940–943 (2008)ADSCrossRefGoogle Scholar
  5. 5.
    F.A. Gallagher, M.I. Kettunen, D.E. Hu, P.R. Jensen, R.I. Zandt, M. Karlsson, A. Gisselsson, S.K. Nelson, T.H. Witney, S.E. Bohndiek, G. Hansson, T. Peitersen, M.H. Lerche, K.M. Brindle, Proc. Natl. Acad. Sci. USA. 106(47), 19801–19806 (2009)Google Scholar
  6. 6.
    P.R. Jensen, T. Peitersen, M. Karlsson, R. in ‘t Zandt, A. Gisselsson, G. Hansson, S. Meier, M.H. Lerche, J. Biol. Chem. 284(52), 36077–36082 (2009)Google Scholar
  7. 7.
    M. Karlsson, P.R. Jensen, R. in ‘t Zandt, A. Gisselsson, G. Hansson, J.O. Duus, S. Meier, M.H. Lerche, Int. J. Cancer 127(3), 729–736 (2010)CrossRefGoogle Scholar
  8. 8.
    F.A. Gallagher, M.I. Kettunen, S.E. Day, D.E. Hu, M. Karlsson, A. Gisselsson, M.H. Lerche, K.M. Brindle, Magn. Reson. Med. 66(1), 18–23 (2011)CrossRefGoogle Scholar
  9. 9.
    F.A. Gallagher, M.I. Kettunen, S.E. Day, M. Lerche, K.M. Brindle, Magn. Reson. Med. 60(2), 253–257 (2008)CrossRefGoogle Scholar
  10. 10.
    S. Meier, P.R. Jensen, J.O. Duus, FEBS Lett. 585(19), 3133–3138 (2011)CrossRefGoogle Scholar
  11. 11.
    S. Meier, P.R. Jensen, J.O. Duus, ChemBioChem 13(2), 308–310 (2012)CrossRefGoogle Scholar
  12. 12.
    S. Meier, M. Karlsson, P.R. Jensen, M.H. Lerche, J.O. Duus, Mol. BioSyst. 7(10), 2834–2836 (2011)CrossRefGoogle Scholar
  13. 13.
    J.H. Ardenkjær-Larsen, B. Fridlund, A. Gram, G. Hansson, L. Hansson, M.H. Lerche, R. Servin, M. Thaning, K. Golman, Proc. Nat. Acad. Sci. USA. 100(18), 10158–10163 (2003)ADSCrossRefGoogle Scholar
  14. 14.
    C.A. Angell, E.J. Sare, J. Chem. Phys. 52(3), 1058–1068 (1970)ADSCrossRefGoogle Scholar
  15. 15.
    C.A. Angell, R.D. Bressel, J.L. Green, H. Kanno, M. Oguni, E.J. Sare, J. Food Eng. 22(1–4), 115–142 (1994)CrossRefGoogle Scholar
  16. 16.
    Y. Yoshimura, A. Onishi, H. Kanno, J. Solut. Chem. 28(10), 1127–1136 (1999)CrossRefGoogle Scholar
  17. 17.
    E.I. Bunyatova, Nucl. Instrum. Methods Phys. Res. Sect. A Accel. Spectrom. Detect. Assoc. Equip. 356(1), 29–33 (1995)ADSCrossRefGoogle Scholar
  18. 18.
    B. Eichelman, N.B. Thoa, J. Perez-Cruet, Pharmacol. Biochem. Behav. 1(1), 121–123 (1973)CrossRefGoogle Scholar
  19. 19.
    R.R. Fieve, H. Meltzer, D.L. Dunner, M. Levitt, J. Mendlewicz, A. Thomas, Am. J. Psychiatry 130(1), 55–61 (1973)Google Scholar
  20. 20.
    P.O. Ettinger, T.J. Regan, H.A. Oldewurtel, Am. Heart J. 88(3), 360–371 (1974)CrossRefGoogle Scholar
  21. 21.
    D.H. Lawson, Q. J. Med. 43(171), 433–440 (1974)Google Scholar
  22. 22.
    G.T. Johnson, T.R. Lewis, W.D. Wagner, Toxicol. Appl. Pharmacol. 32(2), 239–245 (1975)CrossRefGoogle Scholar
  23. 23.
    Z. Gottesfeld, Psychopharmacologia 45(3), 239–242 (1976)CrossRefGoogle Scholar
  24. 24.
    V. Yap, A. Patel, J. Thomsen, JAMA 236(24), 2775–2776 (1976)CrossRefGoogle Scholar
  25. 25.
    L. Lumata, Z. Kovacs, C. Malloy, A.D. Sherry, M. Merritt, Phys. Med. Biol. 56(5), N85–N92 (2011)ADSCrossRefGoogle Scholar
  26. 26.
    T.E. Needham Jr, A.N. Paruta, R.J. Gerraughty, J. Pharm. Sci. 60(4), 565–567 (1971)CrossRefGoogle Scholar
  27. 27.
    K.D. Safa, M. Babazadeh, H. Namazi, M. Mahkam, M.G. Asadi, Eur. Polym. J. 40(3), 459–466 (2004)CrossRefGoogle Scholar
  28. 28.
    A.A. Strechan, Y.U. Paulechka, A.V. Blokhin, G.J. Kabo, J. Chem. Thermodyn. 40(4), 632–639 (2008)CrossRefGoogle Scholar
  29. 29.
    F. Franks, Pure Appl. Chem. 65(12), 2527–2537 (1993)CrossRefGoogle Scholar
  30. 30.
    M. Plückthun, C. Bradtke, H. Dutz, R. Gehring, S. Goertz, J. Harmsen, P. Kingsberry, W. Meyer, G. Reicherz, Nucl. Instrum. Methods Phys. Res. Sect. A Accel. Spectrom. Detect. Assoc. Equip. 400(1), 133–136 (1997)ADSCrossRefGoogle Scholar
  31. 31.
    P. Mieville, P. Ahuja, R. Sarkar, S. Jannin, P.R. Vasos, S. Gerber-Lemaire, M. Mishkovsky, A. Comment, R. Gruetter, O. Ouari, P. Tordo, G. Bodenhausen, Angew. Chem. Int. Ed. Engl. 49(35), 6182–6185 (2010)CrossRefGoogle Scholar
  32. 32.
    A.E. Dementyev, D.G. Cory, C. Ramanathan, Phys. Rev. Lett. 100(12), 127601 (2008)ADSCrossRefGoogle Scholar
  33. 33.
    L. Laffel, Diabetes Metab. Res. Rev. 15(6), 412–426 (1999)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Magnus Karlsson
    • 1
  • Pernille R. Jensen
    • 1
  • Jens Ø. Duus
    • 2
  • Sebastian Meier
    • 2
  • Mathilde H. Lerche
    • 1
    Email author
  1. 1.Albeda ResearchCopenhagen VDenmark
  2. 2.Carlsberg LaboratoryCopenhagen VDenmark

Personalised recommendations