ET-72 * THE STRATEGY STUDY OF ENHANCED ALA-INDUCED PpIX FLUORESCENT QUALITY IN MALIGNANT GLIOMAS

Abstract

OBJECTIVE: Gliomas are characterized by its local invasiveness and poor prognosis. It has been demonstrated that the survival benefit is associated with the extent of surgical resection. But it is difficult to distinguish tumor margins due to the infiltrative nature, and gliomas often recur within 2-3 cm from the borders of the resection cavity. Recently, fluorescence-guided resection has been demonstrated to improve discrimination of tumor tissue and increase the extent of surgical resection. However, insufficient protoporphyrin IX accumulation may limit the benefits of FGR in low-grade glioma and the marginal area. METHODS: We investigated the expression of the ATP-binding cassette transporter ABCB6 in gliomas, and the correlation between ABCB6 expression and PpIX accumulation. Meanwhile, Glioma cells and astrocytes were preconditioned with calcitriol or arsenic trioxide. Changes in ALA-induced PpIX fluorescence were assessed by flow cytometry and fluorescence microscopy. Furthermore, expression of porphyrin synthetic enzymes in pretreated glioma cells was analyzed. RESULTS: The expression levels of ABCB6 significantly elevated in gliomas, A previously finding was the fact that ABCB6 mRNA expression in solidly fluorescing tumor tissues was significantly higher than that in vaguely fluorescing tumors, Accordingly, ABCB6 overexpression in cell lines increased ALA-induced PpIX accumulation and fluorescent quality. Meanwhile, calcitriol or arsenic trioxide can be administered prior to ALA as a non-toxic preconditioning regimen to significantly enhance ALA- induced PpIX levels and fluorescence. This increase in PpIX level was detected preferentially in glioma versus normal cells. Moreover, mechanistic studies documented that expression of the porphyrin synthesis enzymes coproporphyrinogen oxidase was increased by calcitriol or arsenic trioxide at the mRNA level. CONCLUSIONS: ABCB6 overexpression is a potential approach to enhance accumulation of PpIX for optimising the subjective discrimination of vague fluorescence. We demonstrated for the first time a simple, non-toxic and highly effective preconditioning regimen to selectively enhance PpIX fluorescence in glioma cells.