X-ray fluorescence elemental mapping and microscopy to follow hepatic disposition of a Gd-based magnetic resonance imaging contrast agent

Riccarda Delfino, Matteo Altissimo, Ralf Hendrik Menk, Roberto Alberti, Tomasz Klatka, Tommaso Frizzi, Antonio Longoni, Murielle Salomè, Giuliana Tromba, Fulvia Arfelli, Milan Clai, Lisa Vaccari, Vito Lorusso, Claudio Tiribelli, Lorella Pascolo

Research output: Contribution to journalArticle

Abstract

1.Spatially resolved X-ray fluorescence (XRF) spectroscopy with synchrotron radiation is a technique that allows imaging and quantification of chemical elements in biological specimens with high sensitivity. In the present study, we applied XRF techniques at a macro and micro level to carry out drug distribution studies on ex vivo models to confirm the hepatobiliary disposition of the Gd-based magnetic resonance imaging contrast agent B22956/1. 2.Gd presence was selectively quantified allowing the determination of the time dependent disappearance of the drug from blood and its hepatic accumulation in mice after administration. Elemental mapping highlighted the drug distribution differences between healthy and diseased livers. XRF microanalyses showed that in CCl 4-induced hepatitis, B22956/1 has greatly reduced hepatic accumulation, shown as a 20-fold reduction of Gd presence. Furthermore, a significant increase of Fe presence was found in steatotic compared with healthy livers, in line with the disease features. 3.The present results show that XRF might be useful in preclinical pharmacological studies with drugs containing exogenous elements. Furthermore, quantitative and high-sensitivity elemental mapping allows simultaneous detection of chemical variation, showing pathological conditions. This approach was useful in suggesting reduced B22956/1 accumulation in steatotic livers, thus opening possible new diagnostic perspectives for this drug.

Original languageEnglish
Pages (from-to)834-845
Number of pages12
JournalClinical and Experimental Pharmacology and Physiology
Volume38
Issue number12
DOIs
Publication statusPublished - Dec 2011

Keywords

  • Chemical imaging
  • Liver
  • Magnetic resonance imaging contrast agents
  • X-ray fluorescence

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology

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  • Cite this

    Delfino, R., Altissimo, M., Menk, R. H., Alberti, R., Klatka, T., Frizzi, T., Longoni, A., Salomè, M., Tromba, G., Arfelli, F., Clai, M., Vaccari, L., Lorusso, V., Tiribelli, C., & Pascolo, L. (2011). X-ray fluorescence elemental mapping and microscopy to follow hepatic disposition of a Gd-based magnetic resonance imaging contrast agent. Clinical and Experimental Pharmacology and Physiology, 38(12), 834-845. https://doi.org/10.1111/j.1440-1681.2011.05618.x