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In Vivo Imaging of Muscarinic Cholinergic Receptors in Temporal Lobe Epilepsy with a New PET Tracer: [⁷⁶Br]4-Bromodexetimide

CEA, SHFJ, Orsay
Epilepsy Unit and Urgences Cérébrovasculaires, Clinique P. Castaigne, Hôpital de la Salpêtrière, Paris, France

Correspondence: For correspondence or reprints contact: Sophie Dupont, MD, CEA, SHFJ, 4 place du Gal Leclerc, 91401 Orsay, France.

ABSTRACT

Muscarinic acetyl cholinergic receptors (mAChRs) may be involved in the pathophysiology of partial epilepsy. Previous experimental and imaging studies have reported medial temporal abnormalities of mAChR in patients with medial temporal lobe epilepsy (MTLE). Suitable radiotracers for mAChR are required to evaluate these disturbances in vivo using PET. Dexetimide is a specific mAChR antagonist that has been labeled recently with ⁷⁶Br. This first study in humans focused on regional distribution and binding kinetics of [⁷⁶Br]4-bromodexetimide (BDEX) in patients with MTLE. Methods: Ten patients with well-lateralized MTLE had combined MRI, ¹⁸F-fluorodeoxyglucose (FDG) PET and ⁷⁶Br-BDEX PET studies. Time-activity curves were generated in PET-defined regions of interest, including the medial, polar and lateral regions of the temporal lobe; the basal ganglia; the external and medial occipital cortex; and the white matter. Results: The highest radioactivity concentration was observed in the basal ganglia and in the cortical regions, whereas radioactivity was lower in the white matter. On late images of PET studies, ⁷⁶Br-BDEX uptake was statistically significantly decreased only in the medial temporal region ipsilateral to the seizure focus (1.37 ± 0.28, P < 0.01) as determined by FDG PET imaging, anatomic MRI and electroencephalogram correlation, compared with the contralateral medial temporal region (1.46 ± 0.31). Conclusion: ⁷⁶Br-BDEX concentration is reduced in the temporal lobe ipsilateral to the seizure focus in patients with MTLE. This preliminary study suggests that ⁷⁶Br-BDEX is a suitable radiotracer for studies of mAChR in humans. Further studies are required to investigate the potential value of ⁷⁶Br-BDEX PET in other neurological disorders with muscarinic disturbances.

Key Words: muscarinic receptors • bromodexetimide • PET • temporal lobe epilepsy