title: 5-ALA Fluorescence in Native Pituitary Adenoma Cell Lines: Resection Control and Basis for Photodynamic Therapy (PDT)?
abstract: OBJECTIVE
  Pituitary adenomas (PA), especially invasive ones, are often not completely resectable. Usage of 5-aminolevulinic acid (5-ALA) for fluorescence guided surgery could improve the rate of total resection and, additionally, open the doors for photodynamic therapy (PDT) in case of unresectable or partially resected PAs. The aim of this study was to investigate the uptake of 5-ALA and the effect of 5-ALA based PDT in cell lines.
  
  
  METHODS
  GH3 and AtT-20 cell lines were incubated with different concentrations of 5-ALA, protoporphyrin IX (PPIX) fluorescence was measured by flow cytometry and fluorescencespectrometry. WST-1 assays were performed to determine the surviving fraction of cells after PDT. PPIX fluorescence intensities and PDT effect of the pituitary adenoma cells were compared to U373MG, a well-known glioblastoma cell line.
  
  
  RESULTS
  Both cell lines showed a 5-ALA dependent intracellular PPIX fluorescence. Significant differences after 24hrs of incubation were observed in AtT-20 cells in comparison to GH3. Regardless of the incubation or metabolism time, there was a proliferation inhibiting effect after PDT, with no statistical significance.
  
  
  CONCLUSIONS
  Since GH3 cells showed a heterogenous uptake of 5-ALA in the flow cytometry profile, but not constantly high concentrations they might have a 5-ALA efflux mechanism, which still needs to be determined. In the case of AtT-20, the cells might need a longer time for the uptake due to their size or slow metabolism. We showed that the different cell lines have different uptake and metabolism mechanisms, which needs to be further investigated. The general uptake of 5-ALA allows the possibility of resection control and PDT for pituitary adenomas. But, the role of PDT for unresectable pituitary adenomas deserves further investigations.
authors: Institute of Neuropathology, University Hospital Muenster, Muenster, Germany.
authors: Andrei
authors: A
authors: Nemes
authors: Department of Neurosurgery, University Hospital Muenster, Muenster, Germany.
authors: Thomas
authors: T
authors: Fortmann
authors: Institute of Neuropathology, University Hospital Muenster, Muenster, Germany.
authors: Stephan
authors: S
authors: Poeschke
authors: Department of Radiotherapy-Radiooncology, University Hospital Muenster, Muenster, Germany.
authors: Burkhard
authors: B
authors: Greve
authors: Department of Neurological Surgery, Ohio State University, Columbus, United States of America.
authors: Daniel
authors: D
authors: Prevedello
authors: Department of Neurosurgery, University Hospital Tuebingen, Tuebingen, Germany.
authors: Antonio
authors: A
authors: Santacroce
authors: Department of Neurosurgery, University Hospital Muenster, Muenster, Germany.
authors: Walter
authors: W
authors: Stummer
authors: Institute of Neuropathology, University Hospital Muenster, Muenster, Germany.
authors: Volker
authors: V
authors: Senner
authors: Department of Neurosurgery, University Hospital Muenster, Muenster, Germany.
authors: Christian
authors: C
authors: Ewelt
mesh_terms: D000236:Adenoma / Q000188:drug therapy* / Q000473:pathology; D000622:Aminolevulinic Acid / Q000737:chemistry / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005453:Fluorescence; D006801:Humans; D010778:Photochemotherapy / Q000379:methods*; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013050:Spectrometry, Fluorescence
chemical_list: D000622:Aminolevulinic Acid