Current Applications of 5-ALA in Glioma Diagnostics and Therapy

Gliomas, the most common primary brain tumors, are characterized by rapid proliferation, marked infiltration, and poor prognosis and are known for their dismal outcomes (Iacob & Din‐ ca, 2009; Lefranc et al., 2006). The infiltrative nature of malignant glioma makes complete resec‐ tion difficult, as tumor margins are unclear. Recurrence of glioma takes place within approximately 2 cm of the margins of the resected cavity owing to its invasive character (Aydin et al., 2001; Wallner et al., 1989). The use of fluorescence to delineate tumor margins intraopera‐ tively has emerged as a safe and effective tool for increasing the extent of resection. Therefore, methods that easily detect tumor margins during surgery would be extremely beneficial. 5-ami‐ nolevulinic acid (5-ALA) fluorescence-guided glioma resection is a rapidly growing, novel ap‐ proach to improve the extent of tumor resection with broad applications in both preclinical and clinical settings (Stummer et al., 2000; Stummer et al., 1998b; Stummer et al., 1998c). Intraopera‐ tive tumor fluorescence provided by the chemical compound 5-ALA assists surgeons in identi‐ fying the true tumor margin during resection of glial neoplasms, consequently increasing the extent of the resection. 5-ALA is the most studied fluorescer and has been used in many clinical trials, including a multicenter phase III randomized controlled trial. Recent controlled Phase III clinical trials have demonstrated that this surgical method enables more complete resection of contrast-enhancing lesions than conventional microsurgery and improves progression-free survival in patients with malignant glioma (Pichlmeier et al., 2008; Stummer et al., 2006).