gms | German Medical Science

Objective: The utility of 5-aminolevulinic acid (5-ALA) mediated fluorescence-guided resection (FGS) of meningiomas is increasingly investigated in both in-vitro and in-vivo studies. However, kinetics of 5-ALA as well as expression of protoporphyrin (Pp) IX transport proteins (ABCG2 and ABCB6) and the Ferrochelatase (FECH) in meningiomas are largely unexplored.

Methods: Immortalized benign Ben-Men1 and malignant IOMM-Lee cells lines as well as primary grade I and II meningioma cells were treated with varying concentration of 5-ALA for 4h. PpIX fluorescence and expression of ABCG2, ABCB6 and FECH were analysed after 0, 2, 4 and 6 hours and compared with U87 glioblastoma cells.

Results: Primary meningioma cells showed similar PpIX fluorescence intensity over time compared to Ben-Men1 and U87 cells after exposure to a medium dose of 5-ALA (50 µg/ml). In contrast to U87, exposure to 100 µg/ml 5-ALA lead to a significant increase of fluorescence in Ben-Men1 cells with a similar trend in primary meningioma cells. On the other hand, IOMM Lee cells did not show any relevant fluorescence. The attached figure illustrates the fluorescence intensity over time following administration of 50 or 100 µg/ml 5-ALA in primary meningioma, Ben-Men1, IOMM LEE and U87 cells (0=immediate measurement after finishing incubation). As a negative control empty 96-well plate wells (no cells) were used.Relative expression of the PpIX importer ABCB6 as well as FECH was increased in Ben-Men and primary meningioma cells compared to U87. Interestingly, also the relative expression level of the PpIX exporter ABCG2 was increased in primary meningioma cells while no expression could be detected in Ben-Men or IOMM-LEE cells.

Conclusion: Ben-Men1 but not IOMM-Lee cells were shown as valid models to study 5-ALA kinetics in immortalized meningioma cells. In contrast to glioblastomas, increase of 5-ALA dosage during FGS of meningiomas might help to overcome frequently reported intraoperative shortcomings such as heterogenous tumor fluorescence and lack of fluorescence of the dura tail. As expression of PpIX metabolism molecules is not necessarily correlated, other molecular mechanisms might alter fluorescence in meningiomas.