The use of 5-ALA in glioma surgery: mechanism of action, clinical benefits, and technical limitations: a narrative review

Aims: Glioblastoma is the most aggressive primary brain tumor, characterized by rapid proliferation and diffuse infiltration into surrounding brain tissue. Maximal safe resection is a critical prognostic factor, yet complete tumor removal remains difficult. This review aims to synthesize current data on the application of 5-aminolevulinic acid (5-ALA) in glioma surgery, with particular emphasis on its mechanism of action, clinical utility, limitations, and integration with other intraoperative imaging techniques. Methods: A narrative review was conducted using the PubMed and Google Scholar databases. The search included combinations of keywords such as "5-ALA," "5-aminolevulinic acid," "glioblastoma," "high-grade glioma," and "neurosurgery." Peer-reviewed English-language articles were selected to examine the clinical and technical aspects of 5-ALA-guided fluorescence imaging in glioma resection. No time restriction or formal inclusion criteria were applied. Results: 5-ALA induces selective fluorescence in malignant glioma tissue, enabling improved intraoperative visualization and facilitating gross total resection. Studies have demonstrated enhanced surgical outcomes, including prolonged progression-free and overall survival in patients undergoing 5-ALA-guided resection. However, limitations include reduced sensitivity in low-grade gliomas, the risk of false-positive or false-negative signals, and dependency on specialized equipment and optical conditions. Adjunctive use with intraoperative MRI and sodium fluorescein has shown preliminary benefits. Off-label applications in non-glioma tumors are under investigation. Conclusions: 5-ALA represents a clinically validated tool for improving tumor delineation and surgical precision in high-grade glioma surgery. Despite certain limitations, especially in low-fluorescence tumors and deep-seated lesions, future research into combined imaging strategies, enhanced metabolic targeting, and photodynamic applications may broaden its clinical utility.