Abstracts

Changes in GABAergic inhibition are known to be associated with epilepsy. Human positron emission tomography (PET) studies have shown altered GABA[sub]A[/sub] receptor expression using flumazenil (FMZ), a ligand with a high affinity for the central benzodiazepine receptor (cBZR). Small animal PET, using serial scans in the same epileptic animal, is potentially a powerful technique to investigate the evolution and pathophysiolgical basis of these changes during epileptogenesis . The aim of this study was to explore the potential of 2[apos]-[18F]fluoroflumazenil ([¹⁸F]FFMZ) to study the GABA[sub]A[/sub]/cBZR complex in rats utilizing small animal PET., In five male non-epileptic control rats (350-375 g), two serial dynamic PET scans were acquired under ketamine/xylazine anaesthesia after bolus injection of [¹⁸F]FFMZ (66.6 [plusmn] 3.7 MBq). Six scans were acquired after injecting a tracer dose. In addition, a pre-saturation scan, consisting of a cold FMZ injection followed 10 min later by [¹⁸F]FFMZ, and two displacement studies (cold FMZ injection during the dynamic scan) were performed. PET/MRI co-registration was performed to delineate different regions of interest (whole brain, hippocampus, pons)., In the hippocampus, a structure with high GABA[sub]A[/sub]/cBZR density, the signal intensity was higher (10%) than in the whole brain (p[lt] 0.05) with no difference between left and right hippocampus. In the pons, which has low GABA[sub]A[/sub]/cBZR density, the signal intensity was approximately 20% lower than in the whole brain (p[lt] 0.01). Pre-saturation and displacement studies showed a high non-specific component in the measured signal, which may be due to recirculation of [¹⁸F]-fluoroethanol, a metabolite of [¹⁸F]FFMZ.[figure1], This study has demonstrated differential uptake of [¹⁸F]FFMZ into key structures in the brain, with the highest activity in the hippocampus. However, significant non-specific activity in the brain will limit the ability to detect changes in GABA[sub]A[/sub]/cBZR density during epileptogenesis and therefore alternative ligands need to be investigated., (Supported by the CRC for Biomedical Imaging Development.)