Quantitative Modulation of PpIX Fluorescence and Improved Glioma Visualization
Open accessAbstract
5-Aminolevulinic acid (5-ALA) induced fluorescence to augment surgical resection for high grade glioma has become a standard of care. Protoporphyrin IX (PpIX) visibility is however subject to the variability of the single tumor expression and to the interobserver interpretation. We therefore hypothesized that in different glioma cell lines with variable 5-ALA induced fluorescence, the signal can be pharmacologically increased. We therefore analyzed in three different GBM cell lines, with different expression of epidermal growth factor receptor (EGFR), the variability of 5-ALA induced PpIX fluorescence after the pharmacological blockade at different steps of PpIX breakdown and influencing the outbound transport of PpIX. Using flow cytometry, fluorescence microplate reader, and confocal microscopy the PpIX fluorescence was analyzed after exposure to tin protoporphyrin IX (SnPP), deferoxamine (DFO), and genistein. We furthermore constructed a microscope (Qp9-microscope) being able to measure quantitatively the concentration of PpIX. These values were compared with the extraction of PpIX in tumor biopsy taken during the GBM surgery. Although all three cell lines showed an increase to 5-ALA induced fluorescence their baseline activity was different. Treatment with either SnPP, DFO and genistein was able to increase 5-ALA induced fluorescence. Qp9-microscopy of tumor sample produced a color coded PpIX concentration map which was overlaid on the tumor image. The PpIX extraction from tumor sample analyzed using the plate reader gave lower values of the concentration, as compared to the expected values of the Qp9-microscope, however still in the same decimal range of μg/mL. This may be due to homogenization of the values during extraction and cell disaggregation. In conclusion pharmacological augmentation in GBM cell lines of PpIX signal is possible. A quantitative PpIX map for surgery is feasible and may help refine surgical excision. Further correlations of tumor tissue samples and Qp9-microscopy is needed, prior to develop an intraoperative surgical adjunct to the already existing 5-ALA induced surgery.
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DFO has been demonstrated to enhance PpIX fluorescence and/or PDT effects in various studies with different cell lines including skin, bladder, and glioblastoma tumor cells.
“DFO has been demonstrated to enhance PpIX fluorescence and/or PDT effects in various studies with different cell lines including skin, bladder, and glioblastoma tumor cells [86,87,88,89,90].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [90]
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- Authors
- Reinert, M., Piffaretti, D., Wilzbach, M., Hauger, C., Guckler, R., Marchi, F., & D'Angelo, M. L.
- Affiliations
- University of Bern (CH)
- Carl Zeiss (Germany) (DE)
- Laboratory for Biomedical Neurosciences (CH)
- Corresponding author
- Reinert, Michael
- Venue
- Frontiers in Surgery
- Publisher
- Frontiers Media SA
- Published
- 2019-07-16
- Volume
- 6
- Pages
- 41-41
- ISSN
- 2296-875X (ISSN-L)
- PMC
- PMC6646670
- OpenAlex
- W2958888922
- Cited by
- 22
- References
- 24
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 7 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 1
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Update notices
- corrigendum (2020-04-02)
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Surgery (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Keywords
- protoporphyrin IX, 5-aminolevulinic acid, glioma, glioblastoma, fluorescence-guided surgery, tin protoporphyrin IX, deferoxamine, genistein, epidermal growth factor receptor, intraoperative imaging
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