Quantitative Modulation of PpIX Fluorescence and Improved Glioma Visualization

Frontiers in Surgery
Michael ReinertMaria Luisa D'Angelo

Abstract

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 activi...Continue Reading

References

Jul 13, 2011·Molecular and Cellular Biochemistry·Tetsuya OginoKozo Utsumi
Nov 16, 2012·Scientific Reports·Pablo A ValdésDavid W Roberts
Aug 2, 2013·Optics Letters·Pablo A ValdesKeith D Paulsen
Apr 15, 2014·ISRN Surgery·Johnathan E LawrenceRobert J Winn
Mar 19, 2015·Frontiers in Oncology·Nicole Renee ParkerHelen Ruth Wheeler
Feb 23, 2017·Photodiagnosis and Photodynamic Therapy·Johan C O RichterKarin Wårdell
May 14, 2017·Journal of Neuro-oncology·Andrea O FontanaMichael Reinert
Nov 18, 2019·Journal of Photochemistry and Photobiology. B, Biology·Deborah PiffarettiMaria Luisa D'Angelo

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Methods Mentioned

BETA
surgical resection
Flow Cytometric
flow cytometry
xenograft
confocal microscopy
Fluorescence
biopsy
imaging techniques

Software Mentioned

BrainLab Buzz
Qp9

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