5-ALA kinetics in meningiomas: analysis of tumor fluorescence and PpIX metabolism in vitro and comparative analyses with high-grade gliomas

J Neurooncol. 2021 Mar;152(1):37-46. doi: 10.1007/s11060-020-03680-9. Epub 2021 Jan 3.

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.

Keywords: 5-Aminolevulinic acid; fluorescence; in-vitro; meningioma.

Publication types

  • Comparative Study

MeSH terms

  • Aminolevulinic Acid / metabolism
  • Aminolevulinic Acid / pharmacokinetics*
  • Cell Line, Tumor
  • Glioma / metabolism
  • Glioma / surgery
  • Humans
  • Kinetics
  • Meningeal Neoplasms / metabolism*
  • Meningeal Neoplasms / surgery
  • Meningioma / metabolism*
  • Meningioma / surgery
  • Optical Imaging / methods*
  • Photosensitizing Agents / metabolism
  • Photosensitizing Agents / pharmacokinetics
  • Protoporphyrins / metabolism*
  • Protoporphyrins / pharmacokinetics
  • Surgery, Computer-Assisted / methods

Substances

  • Photosensitizing Agents
  • Protoporphyrins
  • Aminolevulinic Acid
  • protoporphyrin IX