Artikel
Protoporphyrin IX in serum of glioblastoma patients after 5-ALA administration – a potential biomarker?
Protoporphyrin IX im Serum von Glioblastom Patienten nach Administration von 5-ALA – ein potentieller Biomarker?
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Veröffentlicht: | 25. Mai 2022 |
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Objective: 5-Aminolevulinic acid (5-ALA)-mediated fluorescence-guided resection (FGR) maximizes tumor resection in high-grade glioma surgery, improving progression-free survival. Hereby, tumor tissue is identified by the pink color resulting from protoporphyrin IX (PPIX), which, induced by 5-ALA, accumulates selectively in malignant glioma cells. Tumor cells can produce porphyrins naturally or after administration of their prodrug 5-ALA, which is reflected in elevated plasma levels of cancer patients as shown for colorectal adenocarcinoma, bladder and prostate cancer. The aim of this work was to evaluate if PPIX could serve as a blood biomarker for the tumor burden in glioma patients.
Methods: Liquid chromatography coupled to mass spectrometry (LC-MS) was applied for quantification of PPIX in serum. PPIX levels in patients with primarily diagnosed glioblastoma undergoing FGR were evaluated. Blood was collected from 11 patients before, during and after FGR and from 3 healthy volunteers after 5-ALA administration. PPIX was extracted from serum using liquid-liquid extraction followed by an anionic exchange and measured with target LC-MS with mesoporphyrin IX as internal standard. The project was approved by the local ethics committee.
Results: Healthy volunteers exhibited average PPIX serum levels ranging from 16 to 774 pmol/ml after 5-ALA administration. In the patient group, the PPIX serum level was 2.4-fold higher and peaked at later time points (8.0 h vs. 3.8 h). The time curve of the PPIX level in patients and healthy volunteers was first similar, but started spreading around 4.5 h after 5-ALA administration (Figure 1 [Fig. 1]). Even 48 h after 5-ALA administration the PPIX serum levels were third as high in patients than in healthy probands demonstrating a longer elimination time.
Conclusion: PPIX serum levels following 5-ALA administration increased both in patients and healthy volunteers, but they were higher and peaked later in the former. The time point of the maximal serum PPIX level was in agreement with the time of the highest measured fluorescence in glioma tissue (7-8 h after 5-ALA administration). LC-MS-based analysis is a valuable means of monitoring PPIX ex vivo. Further effort is required to elucidate if PPIX is a blood biomarker for the tumor burden in glioma patients.