11C-Metoclopramide PET in epilepsy (EPIFLUX)

Epilepsy is one of the most common serious neurological disorders, affecting approximately 65 million people worldwide. Epileptic seizures cant be controlled by antiepileptic drugs (AED) in about 30% of the cases resulting in drug-resistant epilepsy (DRE). Many AED are substrates of the major drug transporter P-glycoprotein (P-gp). P-gp is located at the smallest blood vessels in the brain, were usually drugs disperse to the brain tissue. In many cases of DRE high expression of P-gp causes low AED concentrations in the respective brain region. Then, surgical removal of the seizure origin (focus) is often proposed as the final remedy to stop seizures and improve quality of life. Unfortunately the focus cant always be located and its characteristics fully investigated. The EPIFLUX project is led by young scientists and carried out by two multidisciplinary research teams (CEA-SHFJ in Orsay, France and the Medical University of Vienna, Austria). We aim at imaging P-gp transporter function at the human brain with the non-invasive technique 11C-metoclopramide Positron Emission Tomography (PET) imaging to localize and characterize epileptogenic foci associated with DRE. Our ambition is to pave the way for the use of 11C-metoclopramide PET as a diagnostic biomarker to localize and characterize epileptogenic foci associated with DRE and provide much needed information for a targeted management of DRE.

Epilepsy is one of the most common serious neurological disorders. Epileptic seizures can be controlled by antiseizure medications in most cases. However, approximately 30% of patients are drug-resistant and fail to respond to standard medical therapies. The surgical resection of the seizure focus is often the only way to cure these patients. Prior to surgery the exact localization of the seizure focus needs to be determined by means of different diagnostic techniques. There is a need for improved diagnostic techniques. It is known that epileptic seizures lead to an up-regulation of a protein called P-glycoprotein in brain capillaries. This protein can be regionally measured in the brains of patients with an imaging method called positron emission tomography (PET). To this end, a radioactively labelled substance called [11C]metoclopramide is intravenously administered to patients and the distribution of this radioactive substance in the brain is measured with a PET camera. We were able to show in this project that [11C]metoclopramide PET can detect a regionally increased expression of P-glycoprotein in the brains of epilepsy patients. This diagnostic technique may aid in the localization of epileptic foci in the presurgical evaluation of drug-resistant epilepsy patients. Moreover, it may be used to assess whether increased P-gp expression occurs in other neurological diseases.