Artikel
Quantification of 5-aminolevulinic acid fluorescence intensity in human brain tumors – preliminary results
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Veröffentlicht: | 2. Juni 2015 |
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Gliederung
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Objective: Many studies demonstrated that recurrence free survival in patients with glioblastoma or meningioma depends on the extent of tumor resection. Recently, 5-aminolaevulinacid (5-ALA) was introduced for fluorescence-guided resection. However, this method is highly subjective. Furthermore, fluorescence signals may be affected by external factors such as light exposure, distance between light and tumor and surface appearance of the tumor. Recently, a method to quantify fluorescence intensity was described and first clinical evaluations have started. In order to validate this promising method and gather further clinical experience, we built up a similar set-up.
Method: A spectrometer connected to a hand-held fiber optic (diameter ca. 2mm) was used. First, calibration curves with PPIX were registered for validation. Second, fluorescence intensity of 7 glioblastoma samples and 10 meningioma samples were measured ex vivo at distances of 0; 0.5; 1; 1.5 and 2mm, respectively. Proliferation was assessed by Ki67 and correlated with the measured fluorescence intensity.
Results: A linear relationship between PPIX concentration and fluorescence intensity could be demonstrated in the dilution series. Furthermore, glioblastoma showed two-fold higher fluorescence intensity as compared to meningioma. Macroscopically, these differences were not detectable: all were rated as strongly fluorescing. An inverse relationship was found between fluorescence intensity and tumor distance (r=-0,47, p< 0,01; r=-0,51, p < 0,001). No correlation between Ki67 and fluorescence intensity was found.
Conclusions: The spectrophotometer allowed detection of small differences in PPIX concentrations in vitro and in vivo. The method may easily be transferred into the clinical environment. However, the focal character of the probe precludes a "scanning" of the resection margins. Technological progress is necessary to integrate quantitative measuring into clinical practice. Furthermore, prospective clinical trials are warranted to study whether a higher sensitivity of ALA signal analysis may result in clinical advantages for the patient.