Investigation of Cerebral O-(2-[ 18 F]Fluoroethyl)-L-Tyrosine Uptake in Rat Epilepsy Models

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RESEARCH ARTICLE

Investigation of Cerebral O-(2-[18F]Fluoroethyl)-L-Tyrosine Uptake in Rat Epilepsy Models Carina Stegmayr ,1 Rainer Surges,2,3 Chang-Hoon Choi,1 Nicole Burda,1 Gabriele Stoffels,1 Christian Filß,1,4 Antje Willuweit,1 Bernd Neumaier,1 Alexander Heinzel,1,4 N. Jon Shah,1,2,5 Felix M. Mottaghy,4,6 Karl-Josef Langen1,4,5,6 1

Institute of Neuroscience and Medicine (INM-4; INM-5; INM-11), Forschungszentrum Jülich, 52425, Jülich, Germany Department of Neurology, RWTH University Aachen, Aachen, Germany 3 Department of Epileptology, University Hospital Bonn, Bonn, Germany 4 Department of Nuclear Medicine, RWTH University Hospital Aachen, Aachen, Germany 5 JARA - BRAIN - Translational Medicine, Aachen, Germany 6 Centre of Integrated Oncology (CIO), University of Aachen, Bonn, Cologne and Düsseldorf, Germany 2

Abstract Purpose: A recent study reported on high, longer lasting and finally reversible cerebral uptake of O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) induced by epileptic activity. Therefore, we examined cerebral [18F]FET uptake in two chemically induced rat epilepsy models and in patients with focal epilepsy to further investigate whether this phenomenon represents a major pitfall in brain tumor diagnostics and whether [18F]FET may be a potential marker to localize epileptic foci. Procedures: Five rats underwent kainic acid titration to exhibit 3 to 3.5 h of class IV–V motor seizures (status epilepticus, SE). Rats underwent 4× [18F]FET PET and 4× MRI on the following 25 days. Six rats underwent kindling with pentylenetetrazol (PTZ) 3 to 8×/week over 10 weeks, and hence, seizures increased from class I to class IV. [18F]FET PET and MRI were performed regularly on days with and without seizures. Four rats served as healthy controls. Additionally, five patients with focal epilepsy underwent [18F]FET PET within 12 days after the last documented seizure. Results: No abnormalities in [18F]FET PET or MRI were detected in the kindling model. The SE model showed significantly decreased [18F]FET uptake 3 days after SE in all examined brain regions, and especially in the amygdala region, which normalized within 2 weeks. Corresponding signal alterations in T2-weighted MRI were noted in the amygdala and hippocampus, which recovered 24 days post-SE. No abnormality of cerebral [18F]FET uptake was noted in the epilepsy patients. Conclusions: There was no evidence for increased cerebral [18F]FET uptake after epileptic seizures neither in the rat models nor in patients. The SE model even showed decreased [18F]FET uptake throughout the brain. We conclude that epileptic seizures per se do not cause a longer lasting increased [18F]FET accumulation and are unlikely to be a major cause of pitfall for brain tumor diagnostics. Key words: PET, Epilepsy, Rat model, [18F]FET

Correspondence to: Carina Stegmayr; e-mail: [email protected]

Stegmayr C. et al.: Investigation of Cerebral FET Uptake in Rat Epilepsy Models

Introduction Positron emission tomography (PET) using amino acid tracers is an established method fo