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-D03A-butrol, and Gd-DO3A-HP each induced behavioral impa irments, and some animals died within 1 h after injection, Gd-D03A-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-D03A-HP at 3 mmol Gd/ kg was essentially the same as that of animals injected with Gd-DTPA a t the same dose, The neurotoxicity of the contrast agents tested was g raded as follows: Gd-DTPA less than or equal to Gd-DTPA-BMA=Gd-D03A-bu trol <Gd-DO3A-HP.