{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T01:28:56Z","timestamp":1793755736618,"version":"4.6.1"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurooncol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Diffuse lower-grade glioma (DLGG), i.e. WHO grade 2 and 3 tumors, frequently manifests with epileptic seizures, significantly affecting quality of life. While [\n                      <jats:sup>18<\/jats:sup>\n                      F]FET PET is routinely used to assess glioma metabolism, differences between patients with and without glioma-related epilepsy have not yet been assessed systematically. The objective of this study was to assess whether preoperative [\n                      <jats:sup>18<\/jats:sup>\n                      F]FET PET uptake is associated with epileptic seizures at initial presentation in patients with DLGG.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective study included 121 patients with DLGG with preoperative [\n                      <jats:sup>18<\/jats:sup>\n                      F]FET PET (2015\u20132025). [\n                      <jats:sup>18<\/jats:sup>\n                      F]FET uptake parameters were determined in patients with measurable disease according to PET RANO 1.0 criteria. Seizure status was assessed exclusively for seizures occurring before surgery. Statistical analyses included Fisher\u2019s exact test, Mann-Whitney U test, and multivariable logistic regression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seventy-eight patients (64%) demonstrated measurable disease in [\n                      <jats:sup>18<\/jats:sup>\n                      F]FET, of whom 57 (73%) presented with epileptic seizures compared to 17 (40%) in the no-uptake group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). In the measurable disease group, those with seizures exhibited significantly higher median TBR\n                      <jats:sub>max<\/jats:sub>\n                      (3.02; IQR 2.35\u20134.00) and TBR\n                      <jats:sub>mean<\/jats:sub>\n                      (2.2; IQR 1.8\u20132.5) values than those without seizures (TBR\n                      <jats:sub>max<\/jats:sub>\n                      2.4; IQR 2.00\u20133.16, TBR\n                      <jats:sub>mean<\/jats:sub>\n                      1.9; IQR 1.7\u20132.2). The tumor location did not account for the observed association between [\n                      <jats:sup>18<\/jats:sup>\n                      F]FET uptake and seizures (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05). In multivariable analyses, [\n                      <jats:sup>18<\/jats:sup>\n                      F]FET uptake remained independently associated with preoperative seizures (adjusted OR 2.86, 95% CI 1.18\u20137.07;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.020).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings demonstrate an association between [\n                      <jats:sup>18<\/jats:sup>\n                      F]FET uptake and glioma-related epilepsy in DLGG. Further research on amino acid transporter expression and glutamatergic pathways may elucidate underlying mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11060-026-05815-w","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:06:39Z","timestamp":1790852799000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["[18F]FET uptake in diffuse lower-grade IDH-mutant glioma correlates with glioma-related epilepsy"],"prefix":"10.1007","volume":"180","author":[{"given":"Zeynep","family":"\u00d6zdemir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Roll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Stummer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stjepana","family":"Kovac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"M\u00fcther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"issue":"5","key":"5815_CR1","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/S1474-4422(07)70103-5","volume":"6","author":"MS van Breemen","year":"2007","unstructured":"van Breemen MS, Wilms EB, Vecht CJ (2007) Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management. Lancet Neurol May 6(5):421\u2013430. https:\/\/doi.org\/10.1016\/S1474-4422(07)70103-5","journal-title":"Lancet Neurol May"},{"issue":"2","key":"5815_CR2","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1093\/neuonc\/nou130","volume":"17","author":"Y Wang","year":"2015","unstructured":"Wang Y, Qian T, You G et al (2015) Localizing seizure-susceptible brain regions associated with low-grade gliomas using voxel-based lesion-symptom mapping. Neuro Oncol Feb 17(2):282\u2013288. https:\/\/doi.org\/10.1093\/neuonc\/nou130","journal-title":"Neuro Oncol Feb"},{"issue":"4","key":"5815_CR3","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1002\/ana.10712","volume":"54","author":"M Klein","year":"2003","unstructured":"Klein M, Engelberts NH, van der Ploeg HM et al (2003) Epilepsy in low-grade gliomas: the impact on cognitive function and quality of life. Ann Neurol Oct 54(4):514\u2013520. https:\/\/doi.org\/10.1002\/ana.10712","journal-title":"Ann Neurol Oct"},{"issue":"10","key":"5815_CR4","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1038\/nm.2453","volume":"11","author":"SC Buckingham","year":"2011","unstructured":"Buckingham SC, Campbell SL, Haas BR et al (2011) Glutamate release by primary brain tumors induces epileptic activity. Nat Med Sep 11(10):1269\u20131274. https:\/\/doi.org\/10.1038\/nm.2453","journal-title":"Nat Med Sep"},{"issue":"7775","key":"5815_CR5","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1038\/s41586-019-1564-x","volume":"573","author":"V Venkataramani","year":"2019","unstructured":"Venkataramani V, Tanev DI, Strahle C et al (2019) Glutamatergic synaptic input to glioma cells drives brain tumour progression. Nature Sep 573(7775):532\u2013538. https:\/\/doi.org\/10.1038\/s41586-019-1564-x","journal-title":"Nature Sep"},{"issue":"9","key":"5815_CR6","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1093\/neuonc\/noac003","volume":"1","author":"A Mortazavi","year":"2022","unstructured":"Mortazavi A, Fayed I, Bachani M et al (2022) IDH-mutated gliomas promote epileptogenesis through d-2-hydroxyglutarate-dependent mTOR hyperactivation. Neuro Oncol Sep 1(9):1423\u20131435. https:\/\/doi.org\/10.1093\/neuonc\/noac003","journal-title":"Neuro Oncol Sep"},{"issue":"5","key":"5815_CR7","first-page":"776","volume":"47","author":"FW Floeth","year":"2006","unstructured":"Floeth FW, Pauleit D, Sabel M et al (2006) 18F-FET PET differentiation of ring-enhancing brain lesions. J Nucl Med May 47(5):776\u2013782","journal-title":"J Nucl Med May"},{"issue":"9","key":"5815_CR8","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1093\/neuonc\/now058","volume":"18","author":"NL Albert","year":"2016","unstructured":"Albert NL, Weller M, Suchorska B et al (2016) Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas. Neuro Oncol Sep 18(9):1199\u20131208. https:\/\/doi.org\/10.1093\/neuonc\/now058","journal-title":"Neuro Oncol Sep"},{"issue":"3","key":"5815_CR9","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1093\/neuonc\/noad228","volume":"4","author":"NL Albert","year":"2024","unstructured":"Albert NL, Preusser M (2024) Measure what is measurable: PET RANO 1.0 criteria for interpretation of amino acid PET of diffuse gliomas. Neuro Oncol Mar 4(3):401\u2013402. https:\/\/doi.org\/10.1093\/neuonc\/noad228","journal-title":"Neuro Oncol Mar"},{"issue":"8","key":"5815_CR10","doi-asserted-by":"publisher","first-page":"e436","DOI":"10.1016\/S1470-2045(25)00193-7","volume":"26","author":"N Galldiks","year":"2025","unstructured":"Galldiks N, Lohmann P, Aboian M et al (2025) Update to the RANO working group and EANO recommendations for the clinical use of PET imaging in gliomas. Lancet Oncol Aug 26(8):e436\u2013e447. https:\/\/doi.org\/10.1016\/S1470-2045(25)00193-7","journal-title":"Lancet Oncol Aug"},{"key":"5815_CR11","doi-asserted-by":"publisher","unstructured":"M\u00fcther M, K\u00f6nig L, Backhaus P et al (2026) Prognostic value of [18F]FET-PET in diffuse low-grade (grade 2) gliomas after the 2021 classification of CNS tumors. Eur J Nucl Med Mol Imaging. 2026\/02\/01 2026;53(3):1951\u20131961. https:\/\/doi.org\/10.1007\/s00259-025-07543-1","DOI":"10.1007\/s00259-025-07543-1"},{"issue":"3","key":"5815_CR12","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.nucmedbio.2006.01.002","volume":"33","author":"KJ Langen","year":"2006","unstructured":"Langen KJ, Hamacher K, Weckesser M et al (2006) O-(2-[18F]fluoroethyl)-L-tyrosine: uptake mechanisms and clinical applications. Nucl Med Biol Apr 33(3):287\u2013294. https:\/\/doi.org\/10.1016\/j.nucmedbio.2006.01.002","journal-title":"Nucl Med Biol Apr"},{"key":"5815_CR13","doi-asserted-by":"publisher","unstructured":"Cai L, Kirchleitner SV, Zhao D et al (2020) Glioblastoma Exhibits Inter-Individual Heterogeneity of TSPO and LAT1 Expression in Neoplastic and Parenchymal Cells. Int J Mol Sci Jan 17(2). https:\/\/doi.org\/10.3390\/ijms21020612","DOI":"10.3390\/ijms21020612"},{"key":"5815_CR14","doi-asserted-by":"publisher","unstructured":"Habermeier A, Graf J, Sandhofer BF, Boissel JP, Roesch F, Closs EI (2015) System L amino acid transporter LAT1 accumulates O-(2-fluoroethyl)-L-tyrosine (FET). Amino Acids. Feb;47(2):335\u2009\u2013\u200944. https:\/\/doi.org\/10.1007\/s00726-014-1863-3","DOI":"10.1007\/s00726-014-1863-3"},{"key":"5815_CR15","doi-asserted-by":"publisher","unstructured":"Galldiks N, Lohmann P, Fink GR, Langen KJ (2023) Amino acid PET in neurooncology. J Nucl Med 64(5):693\u2013700. https:\/\/doi.org\/10.2967\/jnumed.122.264859","DOI":"10.2967\/jnumed.122.264859"},{"issue":"1","key":"5815_CR16","doi-asserted-by":"publisher","first-page":"129","DOI":"10.2967\/jnumed.116.176610","volume":"58","author":"M Hutterer","year":"2017","unstructured":"Hutterer M, Ebner Y, Riemenschneider MJ et al (2017) Epileptic Activity Increases Cerebral Amino Acid Transport Assessed by 18F-Fluoroethyl-l-Tyrosine Amino Acid PET: A Potential Brain Tumor Mimic. J Nucl Med Jan 58(1):129\u2013137. https:\/\/doi.org\/10.2967\/jnumed.116.176610","journal-title":"J Nucl Med Jan"},{"issue":"3","key":"5815_CR17","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1007\/s00259-018-4207-9","volume":"46","author":"I Law","year":"2019","unstructured":"Law I, Albert NL, Arbizu J et al (2019) Joint EANM\/EANO\/RANO practice guidelines\/SNMMI procedure standards for imaging of gliomas using PET with radiolabelled amino acids and [(18)F]FDG: version 1.0. Eur J Nucl Med Mol Imaging Mar 46(3):540\u2013557. https:\/\/doi.org\/10.1007\/s00259-018-4207-9","journal-title":"Eur J Nucl Med Mol Imaging Mar"},{"issue":"2","key":"5815_CR18","doi-asserted-by":"publisher","first-page":"E6","DOI":"10.3171\/2023.11.FOCUS23678","volume":"56","author":"BC Bono","year":"2024","unstructured":"Bono BC, Ninatti G, Riva M et al (2024) The role of preoperative [11\u00a0C]methionine PET in defining tumor-related epilepsy and predicting short-term postoperative seizure control in temporal lobe low-grade gliomas. Neurosurg Focus Feb 56(2):E6. https:\/\/doi.org\/10.3171\/2023.11.FOCUS23678","journal-title":"Neurosurg Focus Feb"},{"issue":"1","key":"5815_CR19","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1111\/j.1528-1167.2010.02754.x","volume":"52","author":"BS Kasper","year":"2011","unstructured":"Kasper BS, Struffert T, Kasper EM et al (2011) 18Fluoroethyl-L-tyrosine-PET in long-term epilepsy associated glioneuronal tumors. Epilepsia Jan 52(1):35\u201344. https:\/\/doi.org\/10.1111\/j.1528-1167.2010.02754.x","journal-title":"Epilepsia Jan"},{"issue":"2","key":"5815_CR20","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1007\/s11060-011-0750-y","volume":"107","author":"B Alkonyi","year":"2012","unstructured":"Alkonyi B, Mittal S, Zitron I et al (2012) Increased tryptophan transport in epileptogenic dysembryoplastic neuroepithelial tumors. J Neurooncol Apr 107(2):365\u2013372. https:\/\/doi.org\/10.1007\/s11060-011-0750-y","journal-title":"J Neurooncol Apr"},{"issue":"289","key":"5815_CR21","doi-asserted-by":"publisher","first-page":"289ra86","DOI":"10.1126\/scitranslmed.aaa8103","volume":"27","author":"SM Robert","year":"2015","unstructured":"Robert SM, Buckingham SC, Campbell SL et al (2015) SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma. Sci Transl Med May 27(289):289ra86. https:\/\/doi.org\/10.1126\/scitranslmed.aaa8103","journal-title":"Sci Transl Med May"},{"key":"5815_CR22","doi-asserted-by":"publisher","unstructured":"Milkereit R, Persaud A, Vanoaica L, Guetg A, Verrey F, Rotin D (2015) LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation. Nat Commun. \/05\/22 2015;6(1):7250. https:\/\/doi.org\/10.1038\/ncomms8250","DOI":"10.1038\/ncomms8250"}],"container-title":["Journal of Neuro-Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11060-026-05815-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11060-026-05815-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11060-026-05815-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T01:04:25Z","timestamp":1793754265000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11060-026-05815-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["5815"],"URL":"https:\/\/doi.org\/10.1007\/s11060-026-05815-w","relation":{},"ISSN":["0167-594X","1573-7373"],"issn-type":[{"value":"0167-594X","type":"print"},{"value":"1573-7373","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"20 July 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was approved by the local ethics committee (reference number 2020-091-f-S). The study was conducted in accordance with the 1964 Declaration of Helsinki and its later amendments. The requirement for written informed consent was waived by the local ethics committee due to the retrospective nature of the study.","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable. Due to the retrospective nature of the study and the use of routinely collected clinical data, the requirement for written informed consent was waived by the ethics committee.","order":2,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"1"}}