Neurotoxicity of gadolinium contrast agents for magnetic resonance imaging in rats with osmotically disrupted blood-brain barrier.
The neurotoxicity of intravenously injected Gadolinium (Gd) complexes to rats with disrupted blood-brain barrier (BBB) was evaluated. After disruption of the BBB by infusion of mannitol solution, one of several contrast agents tested was injected intravenously at a dose of 1 or 3 mmol Gd/kg, and neurological symptoms were graded. The concentrations of Gd in brain and plasma were also measured. Injection of Gd-DTPA at a dose of 3 mmol Gd/kg did not change behavior. On the other hand, Gd-DTPA-BMA, Gd-DO3A-butrol, and Gd-DO3A-HP each induced behavioral impairments, and some animals died within 1 h after injection. Gd-DO3A-HP showed lethal effect even at a dose of 1 mmol/kg. The concentration of Gd in the brain of the animals injected with Gd-DO3A-HP at 3 mmol Gd/kg was essentially the same as that of animals injected with Gd-DTPA at the same dose. The neurotoxicity of the contrast agents tested was graded as follows: Gd-DTPA < or = Gd-DTPA-BMA = Gd-DO3A-butrol < Gd-DO3A-HP.
Takahashi
M
M
Research Department, Nihon Schering K.K. 2-6-64, Osaka, Japan.
Tsutsui
H
H
Murayama
C
C
Miyazawa
T
T
Fritz-Zieroth
B
B
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D005682:Gadolinium / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D008353:Mannitol; D009420:Nervous System / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D003287:Contrast Media; D008353:Mannitol; D005682:Gadolinium