title: The biodistribution of [153Gd]Gd-labeled magnetic resonance contrast agents in a transgenic mouse model of renal failure differs greatly from control mice.
abstract: Nephrogenic systemic fibrosis occurs in renally impaired patients who have undergone contrast enhanced MR examination using intravenous gadolinium-based contrast agents. The effect of impaired kidney function on the biodistribution of gadolinium-based contrast agents was investigated using radiolabeled (153/Nat) gadolinium-DOTA, (153/Nat) gadolinium-DTPA, and (153/Nat) gadolinium-DTPA-BMA in a transgenic mouse model of renal impairment. Renally impaired animals had more activity associated with their tissues than did control mice, and this increase varied according to the radiotracer injected. For example, after 7 days, renally impaired animals that received (153/Nat) Gd-DOTA had 3-fold (P < 0.037) more activity in their bone tissue, whereas renally impaired animals receiving (153/Nat) Gd-DTPA and (153/Nat) Gd-DTPA-BMA had 8-fold (P < 0.0001) and 24-fold (P < 0.0001) more activity in their bone tissue, respectively. These findings demonstrate that renal impairment dramatically alters the tissue distribution of Gd(3+) ions in vivo, which are likely a critical factor in the development of nephrogenic systemic fibrosis.
authors.affiliation: Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA. wadast@wustl.edu
authors.forename: Thaddeus J
authors.initials: TJ
authors.lastname: Wadas
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Sherman
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Miner
authors.forename: James R
authors.initials: JR
authors.lastname: Duncan
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Anderson
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005682:Gadolinium / Q000493:pharmacokinetics*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000378:metabolism*; D009394:Nephritis, Hereditary / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D051437:Renal Insufficiency / Q000378:metabolism* / Q000473:pathology; D013045:Species Specificity; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D005682:Gadolinium