Analytical and Bioanalytical Chemistry

, Volume 411, Issue 3, pp 629–637 | Cite as

Complementarity of molecular and elemental mass spectrometric imaging of Gadovist in mouse tissues

  • Sabrina Trog
  • Ahmed H. El-Khatib
  • Sebastian BeckEmail author
  • Marcus R. Makowski
  • Norbert Jakubowski
  • Michael W. Linscheid
Research Paper
Part of the following topical collections:
  1. Elemental and Molecular Imaging by LA-ICP-MS


Drug biodistribution analyses can be considered a key issue in pharmaceutical discovery and development. Here, mass spectrometric imaging can be employed as a powerful tool to investigate distributions of drug compounds in biologically and medically relevant tissue sections. Both matrix-assisted laser desorption ionization–mass spectrometric imaging as molecular method and laser ablation inductively coupled plasma–mass spectrometric imaging as elemental detection method were applied to determine drug distributions in tissue thin sections. Several mouse organs including the heart, kidney, liver, and brain were analyzed with regard to distribution of Gadovist, a gadolinium-based contrast agent already approved for clinical investigation. This work demonstrated the successful detection and localization of Gadovist in several organs. Furthermore, the results gave evidence that gadolinium-based contrast agents in general can be well analyzed by mass spectrometric imaging methods. In conclusion, the combined application of molecular and elemental mass spectrometry could complement each other and thus confirm analytical results or provide additional information.


Matrix-assisted laser desorption ionization–mass spectrometry imaging (MALDI-MSI) Laser ablation inductively coupled plasma–mass spectrometry imaging (LA-ICP-MSI) Gadolinium-based contrast agents (GBCAs) 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures were approved by the guidelines and regulations of the Federation of Laboratory Animal Science Associations (FELASA) and the local guidelines and provisions for implementation of the Animal Welfare Act. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

216_2018_1477_MOESM1_ESM.pdf (2.9 mb)
ESM 1 (PDF 3015 kb)


  1. 1.
    Aime S, Dastru W, Crich SG, Gianolio E, Mainero V. Innovative magnetic resonance imaging diagnostic agents based on paramagnetic Gd (III) complexes. Biopolymers. 2002;66(6):419–28. Scholar
  2. 2.
    Yan GP, Robinson L, Hogg P. Magnetic resonance imaging contrast agents: overview and perspectives. Radiography. 2007;13:e5–e19.CrossRefGoogle Scholar
  3. 3.
    Baranyai Z, Palinkas Z, Uggeri F, Maiocchi A, Aime S, Brucher E. Dissociation kinetics of open-chain and macrocyclic gadolinium (III)-aminopolycarboxylate complexes related to magnetic resonance imaging: catalytic effect of endogenous ligands. Chemistry. 2012;18(51):16426–35. Scholar
  4. 4.
    Kanal E. Gadolinium based contrast agents (GBCA): safety overview after 3 decades of clinical experience. Magn Reson Imaging. 2016;34(10):1341–5. Scholar
  5. 5.
    Aime S, Caravan P. Biodistribution of gadolinium-based contrast agents, including gadolinium deposition. J Magn Reson Imaging. 2009;30(6):1259–67. Scholar
  6. 6.
    Kamaly N, Pugh JA, Kalber TL, Bunch J, Miller AD, McLeod CW, et al. Imaging of gadolinium spatial distribution in tumor tissue by laser ablation inductively coupled plasma mass spectrometry. Mol Imaging Biol. 2010;12(4):361–6. Scholar
  7. 7.
    Lingott J, Lindner U, Telgmann L, Esteban-Fernandez D, Jakubowski N, Panne U. Gadolinium-uptake by aquatic and terrestrial organisms-distribution determined by laser ablation inductively coupled plasma mass spectrometry. Environ Sci Process Impacts. 2016;18(2):200–7. Scholar
  8. 8.
    Aichler M, Huber K, Schilling F, Lohofer F, Kosanke K, Meier R, et al. Spatially resolved quantification of gadolinium (III)-based magnetic resonance agents in tissue by MALDI imaging mass spectrometry after in vivo MRI. Angew Chem Int Ed Engl. 2015;54(14):4279–83. Scholar
  9. 9.
    Moraleja I, Esteban-Fernandez D, Lazaro A, Humanes B, Neumann B, Tejedor A, et al. Printing metal-spiked inks for LA-ICP-MS bioimaging internal standardization: comparison of the different nephrotoxic behavior of cisplatin, carboplatin, and oxaliplatin. Anal Bioanal Chem. 2016;408(9):2309–18. Scholar
  10. 10.
    Scharlach C, Muller L, Wagner S, Kobayashi Y, Kratz H, Ebert M, et al. LA-ICP-MS allows quantitative microscopy of europium-doped iron oxide nanoparticles and is a possible alternative to ambiguous Prussian blue iron staining. J Biomed Nanotechnol. 2016;12(5):1001–10.CrossRefGoogle Scholar
  11. 11.
    Groseclose MR, Castellino S. A mimetic tissue model for the quantification of drug distributions by MALDI imaging mass spectrometry. Anal Chem. 2013;85(21):10099–106. Scholar
  12. 12.
    Becker JS, Becker JS. Imaging of metals, metalloids, and non-metals by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) in biological tissues. Methods Mol Biol. 2010;656:51–82. Scholar
  13. 13.
    Frick DA, Günther D. Fundamental studies on the ablation behaviour of carbon in LA-ICP-MS with respect to the suitability as internal standard. J Anal At Spectrom. 2012;27(8):1294–303.CrossRefGoogle Scholar
  14. 14.
    Austin C, Fryer F, Lear J, Bishop D, Hare D, Rawling T, et al. Factors affecting internal standard selection for quantitative elemental bio-imaging of soft tissues by LA-ICP-MS. J Anal At Spectrom. 2011;26(7):1494–501.CrossRefGoogle Scholar
  15. 15.
    Konz I, Fernandez B, Fernandez ML, Pereiro R, Gonzalez H, Alvarez L, et al. Gold internal standard correction for elemental imaging of soft tissue sections by LA-ICP-MS: element distribution in eye microstructures. Anal Bioanal Chem. 2013;405(10):3091–6. Scholar
  16. 16.
    Hoesl S, Neumann B, Techritz S, Linscheid M, Theuring F, Scheler C, et al. Development of a calibration and standardization procedure for LA-ICP-MS using a conventional ink-jet printer for quantification of proteins in electro- and Western-blot assays. J Anal At Spectrom. 2014;29(7):1282–91.CrossRefGoogle Scholar
  17. 17.
    Bellis DJ, Santamaria-Fernandez R. Ink jet patterns as model samples for the development of LA-ICP-SFMS methodology for mapping of elemental distribution with reference to biological samples. J Anal At Spectrom. 2010;25(7):957–63.CrossRefGoogle Scholar
  18. 18.
    Hoesl S, Neumann B, Techritz S, Sauter G, Simon R, Schlüter H, et al. Internal standardization of LA-ICP-MS immuno imaging via printing of universal metal spiked inks onto tissue sections. J Anal At Spectrom. 2016;31(3):801–8.CrossRefGoogle Scholar
  19. 19.
    Becker JS, Jakubowski N. The synergy of elemental and biomolecular mass spectrometry: new analytical strategies in life sciences. Chem Soc Rev. 2009;38(7):1969–83. Scholar
  20. 20.
    Buck A, Halbritter S, Spath C, Feuchtinger A, Aichler M, Zitzelsberger H, et al. Distribution and quantification of irinotecan and its active metabolite SN-38 in colon cancer murine model systems using MALDI MSI. Anal Bioanal Chem. 2015;407(8):2107–16. Scholar
  21. 21.
    Chumbley CW, Reyzer ML, Allen JL, Marriner GA, Via LE, Barry CE 3rd, et al. Absolute quantitative MALDI imaging mass spectrometry: a case of rifampicin in liver tissues. Anal Chem. 2016;88(4):2392–8. CrossRefGoogle Scholar
  22. 22.
    Lagarrigue M, Lavigne R, Tabet E, Genet V, Thome JP, Rondel K, et al. Localization and in situ absolute quantification of chlordecone in the mouse liver by MALDI imaging. Anal Chem. 2014;86(12):5775–83. CrossRefGoogle Scholar
  23. 23.
    Landgraf RR, Garrett TJ, Conaway MC, Calcutt NA, Stacpoole PW, Yost RA. Considerations for quantification of lipids in nerve tissue using matrix-assisted laser desorption/ionization mass spectrometric imaging. Rapid Commun Mass Spectrom. 2011;25(20):3178–84. CrossRefGoogle Scholar
  24. 24.
    Marsching C, Jennemann R, Heilig R, Grone HJ, Hopf C, Sandhoff R. Quantitative imaging mass spectrometry of renal sulfatides: validation by classical mass spectrometric methods. J Lipid Res. 2014;55(11):2343–53. Scholar
  25. 25.
    Nakanishi T, Takai S, Jin D, Takubo T. Quantification of candesartan in mouse plasma by MALDI-TOFMS and in tissue sections by MALDI-imaging using the stable-isotope dilution technique. Mass Spectrom (Tokyo). 2013;2(1):A0021. Scholar
  26. 26.
    Pirman DA, Reich RF, Kiss A, Heeren RM, Yost RA. Quantitative MALDI tandem mass spectrometric imaging of cocaine from brain tissue with a deuterated internal standard. Anal Chem. 2013;85(2):1081–9. Scholar
  27. 27.
    Schulz S, Gerhardt D, Meyer B, Seegel M, Schubach B, Hopf C, et al. DMSO-enhanced MALDI MS imaging with normalization against a deuterated standard for relative quantification of dasatinib in serial mouse pharmacology studies. Anal Bioanal Chem. 2013;405(29):9467–76. Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Sabrina Trog
    • 1
  • Ahmed H. El-Khatib
    • 1
    • 2
  • Sebastian Beck
    • 1
    Email author
  • Marcus R. Makowski
    • 3
  • Norbert Jakubowski
    • 2
  • Michael W. Linscheid
    • 1
  1. 1.Department of ChemistryHumboldt-Universität zu BerlinBerlinGermany
  2. 2.Bundesanstalt für Materialforschung und –prüfungBerlinGermany
  3. 3.Department of RadiologyCharité – Universitätsmedizin BerlinBerlinGermany

Personalised recommendations