IN-VIVO [C-11] FLUMAZENIL-PET CORRELATES WITH EX-VIVO [H-3]FLUMAZENILAUTORADIOGRAPHY IN HIPPOCAMPAL SCLEROSIS

By using [C-11]flumazenil-positron emission tomography ([C-11]FMZ-PET) , we have previously shown that reductions of central benzodiazepine r eceptors (cBZRs) are restricted to the hippocampus in mesial temporal lobe epilepsy (mTLE) caused by unilateral hippocampal sclerosis (HS). Receptor autoradiographic studies on resected hippocampal specimens fr om the same patients demonstrated loss of cBZRs that was over and abov e loss of neurons in the CA1 subregion. Here, we report the first dire ct comparison of in vivo cBZR binding with [C-11]FMZ-PET and ex vivo b inding using [H-3]FMZ autoradiography. Me applied a magnetic resonance imaging-based method for partial volume effect correction to the PET images of [C-11]FMZ volume of distribution ([C-11]FMZ V-d) Obtained in 10 patients with refractory mTLE due to unilateral, histologically ve rified HS. Saturation autoradiography was performed on the hippocampal specimens obtained from the same patients, allowing calculation of re ceptor availability ([H-3]FMZ B-max). After correction for partial vol ume effect, [C-11]FMZ V-d in the body of the epileptogenic hippocampus was reduced by a mean of 42.1% compared with normal controls. [H-3]FM Z B-max, determined autoradiographically from the same hippocampal tis sue, was reduced by a mean of 42.7% compared with control hippocampi. Absolute in vivo and ex vivo measurements of cBZR binding for the body of the hippocampus were significantly correlated in each individual. Our study demonstrates that reduction of available cBZR on remaining n eurons in HS can be reliably detected in vivo by using [C-11]FMZ-PET a fter correction for partial volume effect.