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 = 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.

• Authors: Markus Hutterer, Yvonne Ebner, Markus J Riemenschneider, Antje Willuweit, Mark McCoy, Barbara Egger, Michael Schröder, Christina Wendl, Dirk Hellwig, Jirka Grosse, Karin Menhart, Martin Proescholdt, Brita Fritsch, Horst Urbach, Guenther Stockhammer, Ulrich Roelcke, Norbert Galldiks, Philipp T Meyer, Karl-Josef Langen, Peter Hau, Eugen Trinka
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 58 Issue 1 Pg. 129-137 (Jan 2017) ISSN: 1535-5667 [Electronic] United States
• PMID: 27469356 (Publication Type: Journal Article)
• Copyright: © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Chemical References

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

Topics

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