Epilepsy Research, 13 (1992) 129-139 0920-121 l/92/$05.00 0 1992 Elsevier Science Publishers B.V. All rights reserved 129 EPIRES 005 13 PET imaging of opiate receptor binding in human epilepsy using [’ 8F]cyclofoxy William H. Theodorea, Richard E. Carsonb, Paul Andreasenc, Allan Zametkin”, Ron Blasbergb, Deborah B. Leiderman”, Kenner Riced, Amy Newmand, Michael Channingb, Bonnie Dunnb, Norman Simpsonb and Peter Herscovitchb zyxwvutsrqponmlkjihgfe “Clinical Epilepsy Section. NINDS, bDepartment of Positron Emission Tomography, Clinical Center, ‘Brain Imaging Section, NIMH and dLaboratory of Medicinal Chemistry, NIDDK. NIH, Bethesda, MD 20892, USA (Received 20 April 1992; revision received 15 June 1992; accepted I5 June 1992) Key words: Positron emission tomography; [‘sF]Cyclofoxy; Complex partial seizure We used [“Flcyclofoxy (CF), a potent opiate antagonist with affinity for mu and kappa receptors, and the Scanditronix PC1024-7B PET scanner to study 14 patients with complex partial seizures (CPS), and 14 normal controls. Epileptic foci were localized by prolonged EEG-video monitoring. EEG was recorded continuously during each scan. Immediately before CF administration, [“O]labeled water was used to measure cerebral blood flow, and showed hypoperfusion ipsilateral to the EEG focus. Blood samples (corrected for radiolabeled metabolites) and tissue time-activity data were acquired over 90 min following bolus CF injection. Anatomic regions were outlined directly on the PET images. A kinetic model was used to derive the total volume of distribution (I’,) in each brain region. Specific binding (V,) was determined by subtracting non-specific binding (Vr) measured in a receptor-poor brain region (occipital cortex). Regions with high V, included mesial temporal lobes, thalamus, basal ganglia, and frontal cortex. Individual patients appeared to have higher binding in temporal lobe ipsilateral to the EEG focus, but there was no asymmetry for the patients as a group in mean I’, or V, in anterior mesial, posterior mesial, anterior lateral, posterior lateral temporal cortex, thalamus, basal ganglia, or, for I’i, in regions of low specific binding: occipital lobe, parietal lobe, cerebellum. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Introduction Patients with complex partial seizures (CPS) of temporal lobe origin have reduced cerebral blood flow (CBF) and glucose metabolism (LCMRglc), as demonstrated by positron emission tomography (PET); focal gliosis and neuronal loss can be dem- onstrated by pathological examination and MRI scan36. Nevertheless, links between structural and functional abnormalities, and the underlying Correspondence to: William H. Theodore, MD, NIH 10/5N- 248, Bethesda, MD 20892, USA. pathophysiologic process, remain obscure. PET can be used to image putative neurotrans- mitters, and the results of recent studies have sug- gested that receptor number or binding potential for benzodiazepines may be reduced, and opiates increased, in human temporal lobe epileptic foci’3,32. Using [“Clcarfentanil, a highly specific mu opiate receptor ligand, and positron emission tomography, Frost et al.13 found an increase in either the number of unoccupied receptors or re- ceptor affinity in lateral temporal cortex ipsilateral to EEG foci in patients with CPS. LCMRglc mea- sured with 2-[18F]fluorodeoxyglucose correlated in-