Epileptic activity increases cerebral amino acid transport assessed by 18f-fluoroethyl-L-Tyrosine amino acid PET: A potential brain tumor mimic

Abstract

O-(2-18F-fluoroethyl)-L-Tyrosine (18F-FET) PET is a well-established method increasingly used for diagnosis, treatment planning, and monitoring in gliomas. Epileptic activity, frequently occurring in glioma patients, can influence MRI findings. Whether seizures also affect 18F-FET PET imaging is currently unknown. The aim of this retrospective analysis was to investigate the brain amino acid metabolism during epileptic seizures by 18F-FET PET and to elucidate the pathophysiologic background. Methods: Ten patients with 11 episodes of serial seizures or status epilepticus, who underwent MRI and 18F-FET PET, were studied. The main diagnosis was glioma World Health Organization grade II-IV (n 5 8); 2 patients suffered from nonneoplastic diseases. Immunohistochemical assessment of LAT1/ LAT2/CD98 amino acid transporters was performed in seizure-Affected cortex (n 5 2) and compared with glioma tissues (n 5 3). Results: All patients exhibited increased seizure-Associated strict gyral 18FFET uptake, which was reversible in follow-up studies or negative shortly before and without any histologic or clinical signs of tumor recurrence. 18F-FET uptake corresponded to structural MRI changes, compatible with cortical vasogenic and cytotoxic edema, partial contrast enhancement, and hyperperfusion. Patients with prolonged postictal symptoms lasting up to 8 wk displayed intensive and widespread (1 lobe) cortical 18F-FET uptake. LAT1/ LAT2/CD98 was strongly expressed in neurons and endothelium of seizure-Affected brains and less in reactive astrocytosis. Conclusion: Seizure activity, in particular status epilepticus, increases cerebral amino acid transport with a strict gyral 18F-FET uptake pattern. Such periictal pseudoprogression represents a potential pitfall of 18F-FET PET and may mimic brain tumor. Our data also indicate a seizure-induced upregulation of neuronal, endothelial, and less astroglial LAT1/LAT2/CD98 amino acid transporter expression.