BIMG-17. EFFECTS OF THE TUMOUR MICROENVIRONMENT ON PROTOPORPHYRIN IX ACCUMULATION IN GLIOBLASTOMA

Abstract

Glioblastoma is the most common primary brain tumour and has a poor prognosis. The median survival is less than two years despite clinical intervention that usually involves the resection of the tumour volume, chemotherapy and radiotherapy. Achieving gross-total resection is challenging due to poorly defined boundaries as a result of tumour infiltration. Fluorescence-guided surgery (FGS) utilises an apparently selective accumulation of protoporphyrin IX (PPIX) that occurs in areas of glioblastoma after administration of the metabolite, 5-aminolevulinic acid (5-ALA). 5-ALA and the fluorescent metabolite, PPIX, sit within the endogenous heme biosynthetic pathway, which suggests that FGS is not only an important clinical tool, but also highlights differing metabolic phenotypes naturally present throughout the tumour. Genetic and mechanistic studies into this phenomenon have shown that differential expression of metabolite transporters, altered activity of the heme pathway enzymes and variable nutrient availability are all factors in the accumulation of PPIX. However, little is known about the cellular driving force for the uptake of 5-ALA and subsequent conversion into PPIX. Our data suggest that different microenvironments within the tumour alter the activity of the heme biosynthetic pathway, resulting in differential fluorescence in glioblastoma. It paves the way for work to alter the glioblastoma microenvironment in order to further improve the use of FGS in guiding surgery across these devastating tumours.