Molecular and Metabolic Mechanisms Underlying Selective 5-Aminolevulinic Acid-Induced Fluorescence in Gliomas

Abstract

5-aminolevulinic acid (5-ALA) is a porphyrin precursor in the heme synthesis pathway. When supplied exogenously, certain cancers consume 5-ALA and convert it to the fluorogenic metabolite protoporphyrin IX (PpIX), causing tumor-specific tissue fluorescence. Preoperative administration of 5-ALA is used to aid neurosurgical resection of high-grade gliomas such as glioblastoma, allowing for increased extent of resection and progression free survival for these patients. A subset of gliomas, especially low-grade tumors, do not accumulate PpIX intracellularly or readily fluoresce upon 5-ALA administration, making gross total resection difficult to achieve in diffuse lesions. We review existing literature on 5-ALA metabolism and PpIX accumulation to explore potential mechanisms of 5-ALA-induced glioma tissue fluorescence. Targeting the heme synthesis pathway and understanding its dysregulation in malignant tissues could aid the development of adjunct therapies to increase intraoperative fluorescence after 5-ALA treatment.

Evaluation of a Novel Three-Dimensional Robotic Digital Microscope (Aeos) in Neurosurgery

“…First, the visualization of tumor tissue and its discernment from healthy tissue is of utmost importance during neurooncological procedures. The introduction of 5-ALA-induced fluorescence has been a major scientific achievement in the intraoperative visualization of malignant tissue, which is independent of brain shift [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. In conventional microscopic surgery, tumor tissue “glows” after preoperatively administered 5-ALA and intraoperative switching from conventional white light to a blue light source, which is integrated into the microscope.…”

Mutational profiling of low‐grade gliomas identifies prognosis and immunotherapy‐related biomarkers and tumour immune microenvironment characteristics

“…5 Virtually, all LGG finally will be malignantly transformed to HGG. 24 Seizure is the initial symptom of patients with LGG that seriously threatens human life quality. 4 Thus, identifying novel LGG-related molecular mechanisms and finding effective molecular targeted therapies play an important role in improving the survival quality of patients with LGG.…”

“…LGG was characterized by slow progress and malignant transformation potential 5 . Virtually, all LGG finally will be malignantly transformed to HGG 24 . Seizure is the initial symptom of patients with LGG that seriously threatens human life quality 4 .…”

Fluorescence-Guided Surgery in the Surgical Treatment of Gliomas: Past, Present and Future

“…Where 5-ALA-induced fluorescence is observed, it may be a marker for malignant transformation [ 68 ]. The reasons for this dramatic difference in uptake between high- and low-grade gliomas remain unclear; it is proposed that they are due to differences in cellular metabolic activity, membrane transport and local blood–brain barrier permeability [ 69 ].…”