title: The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors.
abstract: BACKGROUND
  Approximately 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.
  
  
  OBJECTIVE
  The 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.
  
  
  METHODS
  Patients 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.
  
  
  RESULTS
  Of 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.
  
  
  CONCLUSIONS
  Age, 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.
authors.affiliation: ‡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.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Jaber
authors.forename: Johannes
authors.initials: J
authors.lastname: Wölfer
authors.forename: Christian
authors.initials: C
authors.lastname: Ewelt
authors.forename: Markus
authors.initials: M
authors.lastname: Holling
authors.forename: Martin
authors.initials: M
authors.lastname: Hasselblatt
authors.forename: Thomas
authors.initials: T
authors.lastname: Niederstadt
authors.forename: Tarek
authors.initials: T
authors.lastname: Zoubi
authors.forename: Matthias
authors.initials: M
authors.lastname: Weckesser
authors.forename: Walter
authors.initials: W
authors.lastname: Stummer
mesh_terms: D000368:Aged; D000622:Aminolevulinic Acid; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005260:Female; D005453:Fluorescence; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading / Q000379:methods; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000494:pharmacology; D014443:Tyrosine
chemical_list: D019275:Radiopharmaceuticals; D014443:Tyrosine; D000622:Aminolevulinic Acid; D019853:O(6)-Methylguanine-DNA Methyltransferase