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.
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