5-ALA kinetics in meningiomas: analysis of tumor fluorescence and PpIX metabolism in vitro and comparative analyses with high-grade gliomas
Abstract
Introduction Although the utility 5-aminolevulinic acid (5-ALA)-mediated fluorescence-guided surgery (FGS) in meningiomas is increasingly discussed, data about the kinetics of protoporphyrin IX (PpIX) and tumor fluorescence are sparse. Methods PpIX kinetics after exposition to varying 5-ALA doses (12.5-150 µg/ml) was analyzed in two immortalized as well as primary WHO grade I and II meningioma and U87 high-grade glioma cell lines. Expression of FECH, ABCB6 and ABCG2 was investigated by quantitative real-time PCR. Results Fluorescence in Ben-Men 1 and primary WHO grade I/II meningioma increased with rising 5-ALA doses up to 100 µg/ml but then showed a saturation effect. However, decrease of fluorescence was slower after 150 than after 100 µg/ml 5-ALA. Fluorescence in U87 cells marginally increased with rising 5-ALA doses. Kinetics of the fluorescence in Ben-Men 1 cells did not differ from primary meningioma cells after 25-150 µg/ml 5-ALA (p > .05, each). No difference was found when comparing the fluorescence between primary grade I and II meningiomas after any 5-ALA dosage (p > .05, each). No relevant fluorescence was found in IOMM-Lee cells. Expression of FECH, ABCB6 and ABCG2 as well as PpIX export differed between all analyzed cell lines but were not connected to fluorescence. Conclusions Eligibility of established meningioma cell lines for in-vitro analyzes of tumor fluorescence significantly differs. Fluorescence in Ben-Men 1 and primary meningioma cell lines but less in IOMM Lee cells is 5-ALA dose-dependent, encouraging in-situ trials to encounter currently discussed shortcomings of FGS in meningiomas. Fluorescence is not related to expression of FECH, ABCB6 and ABCG2.
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Reduced tumor FECH activity is so far the most common answer to the question of the biological basis of selective ALA-induced PpIX tumor disposition, although recent studies have failed to establish a correlation between tumor PpIX levels and FECH or any particular heme biosynthesis enzyme and porphyrin transporter.
“Reduced tumor FECH activity is so far the most common answer to this question, although recent studies have failed to establish a correlation between tumor PpIX levels and FECH or any particular heme biosynthesis enzyme and porphyrin transporter [105,127,166].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [166]
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- Authors
- Bunk, E. C., Wagner, A., Stummer, W., Senner, V., & Brokinkel, B.
- Affiliations
- University Hospital Münster (DE)
- Corresponding author
- Brokinkel, Benjamin
- Venue
- Journal of Neuro-Oncology
- Published
- 2021-01-03
- Volume
- 152
- Issue
- 1
- Pages
- 37-46
- ISSN
- 0167-594X (ISSN-L)
- 1573-7373
- OpenAlex
- W3119295065
- Cited by
- 18
- References
- 24
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 2
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuro-Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Walter Schulz Stiftung, Germany
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Health Sciences › Medicine › Epidemiology › Meningioma and schwannoma management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Keywords
- 5-aminolevulinic acid, protoporphyrin IX, meningioma, fluorescence-guided surgery, high-grade glioma, U87 cells, ferrochelatase, ABCB6, ABCG2
- MeSH terms
- Aminolevulinic Acid, Glioma, Humans, Kinetics, Meningeal Neoplasms, Meningioma, Protoporphyrins, Photosensitizing Agents, Surgery, Computer-Assisted, Cell Line, Tumor, Optical Imaging
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