Complementarity of molecular and elemental mass spectrometric imaging of Gadovist™ in mouse tissues
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.
KeywordsMatrix-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.
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.
- 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. https://doi.org/10.1002/chem.201202930.CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1039/c5em00533g.CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1002/anie.201410555.CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1007/s00216-016-9327-0.CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1007/s00216-013-6778-4.CrossRefPubMedGoogle Scholar
- 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
- 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. https://doi.org/10.1007/s00216-014-8237-2.CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1002/rcm.5189. CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1007/s00216-013-7393-0.CrossRefPubMedGoogle Scholar