title: 5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement.
abstract: BACKGROUND
  Because of intratumoral heterogeneity, diffusely infiltrating gliomas that lack significant contrast enhancement on magnetic resonance imaging are prone to tissue sampling error. Subsequent histologic undergrading may delay adjuvant treatments. 5-Aminolevulinic acid (5-ALA) leads to accumulation of fluorescent porphyrins in malignant glioma tissue, and is currently used for resection of malignant gliomas. The aim of this study was to clarify whether 5-ALA might serve as marker for visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement for precise intraoperative tissue sampling.
  
  
  METHODS
  5-ALA was administered in 17 patients with diffusely infiltrating gliomas with nonsignificant contrast enhancement. During glioma resection, positive fluorescence was noted by a modified neurosurgical microscope. Intraoperative topographic correlation of focal 5-ALA fluorescence with maximum (11)C-methionine positron emission tomography uptake (PET(max)) was performed. Multiple tissue samples were taken from areas of positive and/or negative 5-ALA fluorescence. Histopathological diagnosis was established according to World Health Organization (WHO) 2007 criteria. Cell proliferation was assessed for multiregional samples by MIB-1 labeling index (LI).
  
  
  RESULTS
  Focal 5-ALA fluorescence was observed in 8 of 9 patients with WHO grade III diffusely infiltrating gliomas. All 8 of 8 WHO grade II diffusely infiltrating gliomas were 5-ALA negative. Focal 5-ALA fluorescence correlated topographically with PET(max) in all patients. MIB-1 LI was significantly higher in 5-ALA-positive than in nonfluorescent areas within a given tumor.
  
  
  CONCLUSIONS
  The data indicate that 5-ALA is a promising marker for intraoperative visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement. Unaffected by intraoperative brain shift, 5-ALA may increase the precision of tissue sampling during tumor resection for histopathological grading, and therefore optimize allocation of patients to adjuvant treatments.
authors.affiliation: Department of Neurosurgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Widhalm
authors.forename: Stefan
authors.initials: S
authors.lastname: Wolfsberger
authors.forename: Georgi
authors.initials: G
authors.lastname: Minchev
authors.forename: Adelheid
authors.initials: A
authors.lastname: Woehrer
authors.forename: Martin
authors.initials: M
authors.lastname: Krssak
authors.forename: Thomas
authors.initials: T
authors.lastname: Czech
authors.forename: Daniela
authors.initials: D
authors.lastname: Prayer
authors.forename: Susanne
authors.initials: S
authors.lastname: Asenbaum
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Hainfellner
authors.forename: Engelbert
authors.initials: E
authors.lastname: Knosp
mesh_terms: D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007432:Intraoperative Period; D008297:Male; D008875:Middle Aged; D017319:Photosensitizing Agents; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid