Article
Protoporphyrin IX fluorescence and photobleaching during interstitial photodynamic therapy of malignant gliomas for early treatment prognosis
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Published: | May 21, 2013 |
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Objective: Interstitial photodynamic therapy (iPDT) of non-resectable glioblastoma-recurrences using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) appears to be promising. It remained unclear, however, to which extent inter- and intra-tumoral differences of PpIX concentrations influence the efficacy of iPDT. In the current pilot study, we analyzed PpIX concentrations quantitatively and assessed PpIX induced fluorescence and photobleaching intra-operatively.
Method: 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 tumor 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 neuroradiological 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 tumor parts of these patients (mean PpIX uptake per tumor: 1.4 to 3.0 μM). In the other two patients, however, no or only low PpIX uptake (0 to 0.6 μM) could be detected. The patients with strong PpIX uptake showed treatment response and long-term clinical stabilization (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-tumoral PpIX concentrations exhibited pronounced inter- and intra-tumoral variations in glioblastoma, which are directly linked to variable degrees of fluorescence intensity. High intra-tumoral PpIX concentrations with strong fluorescence intensity and complete photobleaching after iPDT seem to be associated with a 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.