Gadobenate dimeglumine and cerebral glucose metabolism. Continuous monitoring of striatal lactate levels in freely moving rats.

PURPOSE: Brain contrast-enhanced MR imaging reflects the leakage of contrast material into the brain tissue due to blood-brain barrier (BBB) disruption. The contact between brain tissue and contrast material requires a high level of neurotolerability of the contrast agent (CA). In the present study, we investigated the neurotolerability of the paramagnetic CA gadobenate dimeglumine, locally applied into the corpus striatum of freely moving rats, by evaluating its potential effects on cerebral glucose metabolism based on lactate levels. MATERIAL AND METHODS: Lactate levels were monitored using a microdialysis technique coupled with an enzyme reaction. A microdialysis probe for extracellular fluid sampling, together with a stainless steel cannula for CA administration, were inserted into the right corpus striatum of rats. Lactate levels were monitored for 2 h after gadobenate dimeglumine administration at 120 nmol/rat, at fixed volume of 1.2 microl. The same volume of artificial cerebrospinal fluid (aCSF) was administered to control rats. RESULTS: Gadobenate dimeglumine did not induce any significant changes in the lactate striatal levels over the 30-min period after administration. Small, but significant, reductions in lactate concentration were found from the 45-min control point after gadobenate dimeglumine administration. Lactate response showed the same pattern in rats given aCSF. CONCLUSION: Gadobenate dimeglumine, intracerebrally administered, did not affect cerebral glucose metabolism in rats as it showed the same behaviour as aCSF on cerebral glucose utilization. The gradual attenuation in the endogenous lactate release observed 45 min after test compound administration is possibly due to a slight reduction in the probe recovery. The present findings confirm the neurotolerability of gadobenate dimeglumine previously shown in behavioural and electrophysiological studies.

Neurotolerability of gadobenate dimeglumine. Evaluation of brain dopamine concentration in freely moving rats by microdialysis.

RATIONALE AND OBJECTIVES: Magnetic resonance imaging with contrast agents (CAs) is a procedure currently used for the diagnosis of neurologic pathologies. These pathologies are often characterized by blood-brain barrier disruptions, which determines a direct contact between CA and brain tissue. For this reason, an accurate assessment of neurotolerability is useful for the development of new CAs. The present study was designed to evaluate the neurotolerability of a new CA for MRI, gadobenate dimeglumine, employing a neurochemical method. The effect of gadobenate dimeglumine on the striatal levels of neurotransmitters was determined. In particular, the brain concentrations of dopamine and dopamine metabolites, 3,4-dihydroxyphenylacetic and homovanillic acid, were measured using microdialysis, after the direct application of gadobenate dimeglumine into the rat corpus striatum. Gadopentetate dimeglumine and gadoteridol were employed as reference compounds. METHODS: A microdialysis probe for brain extracellular fluid sampling and a stainless-steel cannula for CA application were chronically inserted into the right corpus striatum of rats. All CAs were administered at a dose of 5.4 nmol/rat. Dopamine and metabolite concentrations were analyzed using high-performance liquid chromatography. RESULTS: Gadobenate dimeglumine did not induce any significant changes in the extracellular levels of dopamine or dopamine metabolites up to 2 hours after administration. Gadoteridol produced similar results. Gadopentetate dimeglumine caused a moderate but not significant increase in dopamine levels throughout the duration of the experiments. CONCLUSIONS: Gadobenate dimeglumine directly administered into the corpus striatum of freely moving rats did not affect the dopaminergic system. This result demonstrates the safety of gadobenate dimeglumine under the experimental conditions used, thus confirming previous behavioral and electrophysiologic findings.