title: Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery.
abstract: BACKGROUND
  Using 5-aminolevulinic acid (ALA) as an intraoperative fluorescence contrast has been proven to improve the resection of glioblastoma and contribute to prolonged patient survival. ALA accumulates as protoporphyrin IX (PpIX) in the tumor cells and is administered in an advised dose of 20 mg/kg body weight (b.w.) for brain tumor resection using fluorescence surgical microscopes. PpIX fluorescence availability and intensities of a four folds lower ALA dose (5 mg/kgb.w.) has been investigated in glioblastomas and skin using a spectroscopy system adapted for surgical guidance.
  
  
  METHODS
  A total of 30 adult patients diagnosed with high grade gliomas were included in the analysis. ALA was orally administered in doses of 5 mg/kg b.w. (n = 15) dissolved in orange juice or 20 mg/kgb.w. (n = 15) dissolved in water. A fluorescence spectroscopy system with a handheld fiber-optical probe was used for performing the quantitative fluorescence measurements.
  
  
  RESULTS
  The binominal comparison of the diagnostic performance parameters showed no significant statistical difference (p > 0.05). The median fluorescence values in tumor were 2-3 times higher for the high ALA dose group. No PpIX was detected in the skin of the patients in the low dose group (0/4) while PpIX was detected in the skin of the majority of the patients in the high ALA dose group (13/14).
  
  
  CONCLUSIONS
  Application of 5mg/kg ALA was evaluated as equally reliable as the higher dose regarding the diagnostic performance when guidance was performed using a spectroscopic system. Moreover, no PpIX was detected in the skin of the patients.
authors.affiliation: Department of Biomedical Engineering, Linköping University, Linköping 58185, Sweden. Electronic address: neda.haj.hosseini@liu.se.
authors.forename: Neda
authors.initials: N
authors.lastname: Haj-Hosseini
authors.affiliation: Department of Biomedical Engineering, Linköping University, Linköping 58185, Sweden; Department of Neurosurgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping 581 85, Sweden.
authors.forename: Johan C O
authors.initials: JC
authors.lastname: Richter
authors.affiliation: Department of Clinical Pathology and Department of Clinical and Experimental Medicine, Linköping University, Linköping 581 85, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Hallbeck
authors.affiliation: Department of Biomedical Engineering, Linköping University, Linköping 58185, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Wårdell
mesh_terms: D000368:Aged; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001932:Brain Neoplasms / Q000473:pathology / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005453:Fluorescence; D005910:Glioma / Q000473:pathology / Q000601:surgery*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011524:Protoporphyrins / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D013050:Spectrometry, Fluorescence
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
keywords: Fluorescence guided surgery; Protoporphyrin IX; Quantitative; Skin photosensitivity; Spectroscopy