title: X-ray fluorescence elemental mapping and microscopy to follow hepatic disposition of a Gd-based magnetic resonance imaging contrast agent.
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.
authors.affiliation: Centre for Liver Studies, AREA Science Park, University of Trieste, Trieste, Italy.
authors.forename: Riccarda
authors.initials: R
authors.lastname: Delfino
authors.forename: Matteo
authors.initials: M
authors.lastname: Altissimo
authors.forename: Ralf Hendrik
authors.initials: RH
authors.lastname: Menk
authors.forename: Roberto
authors.initials: R
authors.lastname: Alberti
authors.forename: Tomasz
authors.initials: T
authors.lastname: Klatka
authors.forename: Tommaso
authors.initials: T
authors.lastname: Frizzi
authors.forename: Antonio
authors.initials: A
authors.lastname: Longoni
authors.forename: Murielle
authors.initials: M
authors.lastname: Salomè
authors.forename: Giuliana
authors.initials: G
authors.lastname: Tromba
authors.forename: Fulvia
authors.initials: F
authors.lastname: Arfelli
authors.forename: Milan
authors.initials: M
authors.lastname: Clai
authors.forename: Lisa
authors.initials: L
authors.lastname: Vaccari
authors.forename: Vito
authors.initials: V
authors.lastname: Lorusso
authors.forename: Claudio
authors.initials: C
authors.lastname: Tiribelli
authors.forename: Lorella
authors.initials: L
authors.lastname: Pascolo
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D005234:Fatty Liver / Q000175:diagnosis / Q000378:metabolism; D005260:Female; D005682:Gadolinium / Q000493:pharmacokinetics*; D006505:Hepatitis / Q000175:diagnosis / Q000378:metabolism; D007501:Iron / Q000032:analysis; D008099:Liver / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008808:Mice, Inbred CBA; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D013052:Spectrometry, X-Ray Emission / Q000379:methods*
chemical_list: C440468:B-22956-1; D003287:Contrast Media; D009942:Organometallic Compounds; D005682:Gadolinium; D007501:Iron