• Mohammed Jaber, Johannes Wölfer, Christian Ewelt, Markus Holling, Martin Hasselblatt, Thomas Niederstadt, Tarek Zoubi, Matthias Weckesser, and Walter Stummer.
• ‡Department of Neurosurgery, University Hospital Münster, Münster, Germany; §Institute of Neuropathology, University Hospital Münster, Münster, Germany; ¶Institute for Clinical Radiology, University Hospital of Münster, Münster, Germany; ‖Department of Nuclear Medicine, University Hospital of Münster, Münster, Germany.
• Neurosurgery. 2015 Sep 11.

BackgroundApproximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade.ObjectiveThe aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics.MethodsPatients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors.ResultsOf 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted.ConclusionAge, tumor volume, and F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether fluorescence in grade II gliomas identifies a subtype with worse prognosis remains to be determined.Abbreviations5-ALA, 5-aminolevulinic acidCRT, classification and regression treeF-FET PET, 18F-fluoroethyl tyrosine positron emission tomographyFLAIR, fluid-attenuated inversion recoveryGBM, glioblastoma multiformeO-MGMT, methylguanine DNA methyltransferaseROC, receiver-operating characteristicSUV, standardized uptake valueWHO, World Health OrganizationThis is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work, provided it is properly cited. The work cannot be changed in any way or used commercially.

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