Effects of gadopentetate dimeglumine administration after osmotic blood-brain barrier disruption: toxicity and MR imaging findings.

Abstract

Osmotic blood-brain barrier disruption with intraarterial chemotherapy has been shown to be beneficial in the treatment of malignant brain tumors. Imaging blood-brain barrier disruption is necessary to document the extent and degree of disruption and to correlate disruption with drug delivery. The present study evaluated blood-brain barrier disruption with gadopentetate dimeglumine-enhanced MR imaging and the associated toxicity of gadopentetate dimeglumine administration. Blood-brain barrier disruption was performed in seven dogs for imaging analysis and 17 dogs for toxicity evaluation. In the absence of gadopentetate dimeglumine administration, blood-brain barrier disruption could not be imaged. Enhanced MR imaging with a gadopentetate dimeglumine dose of 0.1 mmol/kg provided good images of disruption at an imaging time of 3 hr after disruption. However, when gadopentetate dimeglumine was given intravenously in conjunction with osmotic blood-brain barrier disruption, there was a statistically significant (p = .02) dose-dependent increase in the frequency of seizures, with 50% of the animals who received 0.1 mmol/kg and 75% who received 0.2 mmol/kg developing delayed seizures. Our findings show that, as with ionized iodinated CT contrast agents, gadopentetate dimeglumine is associated with toxicity when used in conjunction with osmotic blood-brain barrier disruption in dogs. Such toxicity may be a contraindication to the use of gadopentetate dimeglumine for monitoring patients with osmotically induced disruption of the blood-brain barrier.