Epileptic Activity Increases Cerebral Amino Acid Transport Assessed by 18F-Fluoroethyl-l-Tyrosine Amino Acid PET: A Potential Brain Tumor Mimic

J Nucl Med. 2017 Jan;58(1):129-137. doi: 10.2967/jnumed.116.176610. Epub 2016 Jul 28.

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 = 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 gyral 18F-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) 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.

Keywords: 18F-FET PET; LAT1/2 expression; epileptic seizure; glioma; status epilepticus.

MeSH terms

  • Adult
  • Aged
  • Amino Acid Transport Systems / metabolism*
  • Amino Acids / metabolism*
  • Biological Transport, Active
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / metabolism
  • Diagnosis, Differential
  • Diagnostic Errors
  • Epilepsy / diagnostic imaging*
  • Epilepsy / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / pharmacokinetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tyrosine / analogs & derivatives*
  • Tyrosine / pharmacokinetics

Substances

  • Amino Acid Transport Systems
  • Amino Acids
  • Radiopharmaceuticals
  • (18F)fluoroethyltyrosine
  • Tyrosine