Maximal safe surgical resection is the gold standard in brain tumor surgery. Fluorescence-guided surgery (FGS) is one of many intraoperative techniques that have been designed with the intention of accomplishing this goal. 5-aminolevulinic acid (5-ALA) is one of the main fluorophores that facilitates FGS in neurosurgical oncology. Multiple different types of brain tumors can take in and metabolize 5-ALA into protoporphyrin IX (PpIX) through the mitochondria heme biosynthesis pathway. PpIX then selectively accumulates in brain tumor cells due to decreased ferrochelatase activity and emits red fluorescence (630–720 nm) when excited with blue light (375–440 nm). This mechanism allows neurosurgeons to better visualize tumor burden and increase extent of resection while preserving non-cancerous brain parenchyma and, specifically, eloquent white matter tracts, if combined with mapping techniques, thereby minimizing morbidity while improving survival. While 5-ALA use is well established in the treatment of high-grade gliomas, its applicability in recurrent high-grade and non-enhancing IDH-mutant low-grade gliomas, as well as non-glial tumors, is less established or limited by certain features of their cellular and molecular biology. This review aims to discuss the current landscape of 5-ALA utility across the diverse range of brain tumors, practical considerations that optimize its current use in neurosurgery, modern clinical limitations of 5-ALA, and how its application can be expanded by combining its use with other techniques that overcome current limitations.
Current and Future Applications of 5-Aminolevulinic Acid in Neurosurgical Oncology
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