title: Protoporphyrin IX fluorescence and photobleaching during interstitial photodynamic therapy of malignant gliomas for early treatment prognosis.
abstract: OBJECTIVE
  Interstitial photodynamic therapy (iPDT) of non-resectable recurrent glioblastoma using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) has shown a promising outcome. It remained unclear, however, to what extent inter- and intra-tumoural differences of PpIX concentrations influence the efficacy of iPDT. In the current pilot study, we analysed PpIX concentrations quantitatively and assessed PpIX induced fluorescence and photobleaching intraoperatively.
  
  
  METHODS
  Five patients harbouring non-resectable glioblastomas were included. ALA (20 or 30 mg/kg body weight) was given 5-8 hours before treatment. Stereotactic biopsies were taken throughout the tumour volume for both histological analysis and determination of PpIX concentrations, which were measured by chemical extraction. Cylindrical light diffusors were stereotactically implanted. Prior to and after irradiation, fluorescence measurements were performed. Outcome measurement was based on clinical and neuro-radiological follow up.
  
  
  RESULTS
  In three patients, a strong PpIX fluorescence was seen before treatment, which was completely photobleached after iPDT. High concentrations of PpIX could be detected in viable tumour parts of these patients (mean PpIX uptake per tumour: 1.4-3.0 µM). In the other two patients, however, no or only low PpIX uptake (0-0.6 µM) could be detected. The patients with strong PpIX uptake showed treatment response and long-term clinical stabilisation (no progression in 29, 30 and 36 months), early treatment failure was seen in the remaining two patients (death after 3 and 9 months).
  
  
  CONCLUSIONS
  Intra-tumoural PpIX concentrations exhibited pronounced inter- and intra-tumoural variations in glioblastoma, which are directly linked to variable degrees of fluorescence intensity. High intra-tumoural PpIX concentrations with strong fluorescence intensity and complete photobleaching after iPDT seem to be associated with favourable outcome. Real-time monitoring of PpIX fluorescence intensity and photobleaching turned out to be feasible and safe and might be employed for early treatment prognosis of iPDT.
authors.affiliation: Laser-Forschungslabor, University Hospital of Munich, Marchioninistraße 23, 81377 Munich, Germany.
authors.forename: Ann
authors.initials: A
authors.lastname: Johansson
authors.forename: Florian
authors.initials: F
authors.lastname: Faber
authors.forename: Gesa
authors.initials: G
authors.lastname: Kniebühler
authors.forename: Herbert
authors.initials: H
authors.lastname: Stepp
authors.forename: Ronald
authors.initials: R
authors.lastname: Sroka
authors.forename: Rupert
authors.initials: R
authors.lastname: Egensperger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Beyer
authors.forename: Friedrich-Wilhelm
authors.initials: FW
authors.lastname: Kreth
mesh_terms: D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005453:Fluorescence; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D038761:Photobleaching; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010865:Pilot Projects; D011446:Prospective Studies; D011524:Protoporphyrins / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX