title: 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 affect18F-FET PET imaging is currently unknown. The aim of this retrospective analysis was to investigate the brain amino acid metabolism during epileptic seizures by18F-FET PET and to elucidate the pathophysiologic background.
  
  
  METHODS
  Ten patients with 11 episodes of serial seizures or status epilepticus, who underwent MRI and18F-FET PET, were studied. The main diagnosis was glioma World Health Organization grade II-IV (n = 8); 2 patients suffered from nonneoplastic diseases. Immunohistochemical assessment of LAT1/LAT2/CD98 amino acid transporters was performed in seizure-affected cortex (n = 2) and compared with glioma tissues (n = 3).
  
  
  RESULTS
  All patients exhibited increased seizure-associated strict gyral18F-FET 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) cortical18F-FET uptake. LAT1/LAT2/CD98 was strongly expressed in neurons and endothelium of seizure-affected brains and less in reactive astrocytosis.
  
  
  CONCLUSIONS
  Seizure activity, in particular status epilepticus, increases cerebral amino acid transport with a strict gyral18F-FET uptake pattern. Such periictal pseudoprogression represents a potential pitfall of18F-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.
authors.affiliation: Department of Neurology, University of Regensburg Medical School, Regensburg, Germany markus.hutterer@gmx.at.|Wilhelm Sander-Neurooncology Unit, University of Regensburg Medical School, Regensburg, Germany.|Department of Neurology and Centre for Cognitive Neuroscience, Christian-Doppler Klinik, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Hutterer
authors.affiliation: Department of Neurology and Centre for Cognitive Neuroscience, Christian-Doppler Klinik, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Ebner
authors.affiliation: Wilhelm Sander-Neurooncology Unit, University of Regensburg Medical School, Regensburg, Germany.|Department of Neuropathology, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Riemenschneider
authors.affiliation: Institute of Neuroscience and Medicine, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Willuweit
authors.affiliation: Department of Radiology and Division of Neuroradiology, Christian-Doppler Klinik, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Mark
authors.initials: M
authors.lastname: McCoy
authors.affiliation: Department of Nuclear Medicine, Landeskrankenhaus Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Egger
authors.affiliation: Department of Neurology, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schröder
authors.affiliation: Department of Radiology and Division of Neuroradiology, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Wendl
authors.affiliation: Department of Nuclear Medicine, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Hellwig
authors.affiliation: Department of Nuclear Medicine, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Jirka
authors.initials: J
authors.lastname: Grosse
authors.affiliation: Department of Nuclear Medicine, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Menhart
authors.affiliation: Wilhelm Sander-Neurooncology Unit, University of Regensburg Medical School, Regensburg, Germany.|Department of Neurosurgery, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Proescholdt
authors.affiliation: Department of Neurology, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Brita
authors.initials: B
authors.lastname: Fritsch
authors.affiliation: Department of Neuroradiology, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Urbach
authors.affiliation: Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Guenther
authors.initials: G
authors.lastname: Stockhammer
authors.affiliation: Department of Neurology and Brain Tumor Center, Cantonal Hospital Aarau, Aarau, Switzerland.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Roelcke
authors.affiliation: Institute of Neuroscience and Medicine, Forschungszentrum Jülich, Jülich, Germany.|Department of Neurology, University of Cologne, Cologne, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Galldiks
authors.affiliation: Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany; and.
authors.forename: Philipp T
authors.initials: PT
authors.lastname: Meyer
authors.affiliation: Institute of Neuroscience and Medicine, Forschungszentrum Jülich, Jülich, Germany.|Department of Nuclear Medicine, University of Aachen, Aachen, Germany.
authors.forename: Karl-Josef
authors.initials: KJ
authors.lastname: Langen
authors.affiliation: Department of Neurology, University of Regensburg Medical School, Regensburg, Germany.|Wilhelm Sander-Neurooncology Unit, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hau
authors.affiliation: Department of Neurology and Centre for Cognitive Neuroscience, Christian-Doppler Klinik, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Eugen
authors.initials: E
authors.lastname: Trinka
mesh_terms: D000328:Adult; D000368:Aged; D026905:Amino Acid Transport Systems / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism*; D001693:Biological Transport, Active; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D003937:Diagnosis, Differential; D003951:Diagnostic Errors; D004827:Epilepsy / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D026905:Amino Acid Transport Systems; D000596:Amino Acids; D019275:Radiopharmaceuticals; C545932:(18F)fluoroethyltyrosine; D014443:Tyrosine
keywords: 18F-FET PET; LAT1/2 expression; epileptic seizure; glioma; status epilepticus