Fluorescence-Guided Surgery for Malignant Glioma: A Review on Aminolevulinic Acid Induced Protoporphyrin IX Photodynamic Diagnostic in Brain Tumors

Fluorescence and Glioma Surgery

“…Therefore, delineation of tumor margins is imperative for the survival of patients. In standard surgery performed under white light, only 13-20% of glioma resections successfully remove the entire tumor [2]. This rate illustrates that neurosurgeons frequently have difficulty discerning between healthy and malignant tissue during surgery.…”

“…One way to counteract brain shift is through intraoperative imaging, especially by utilizing MRI and ultrasound images. Unfortunately, MRI is expensive and time consuming relative to the surgery [2][3]. Utilizing ultrasound imaging during surgery is cheaper, but one must be exceptionally skilled in ultrasound technique to obtain robust images during surgery, and the instruments can interfere greatly with surgery [3].…”

“…It is unclear what mechanism dictates the highly specific accumulation of PpIX in tumor tissue. Some speculate that because tumor cells down-regulate the activity of the ferrochelatase enzyme, which converts PpIX into the non-fluorescent heme product, malignant tissue is able to accumulate PpIX when 5-ALA is introduced exogenously, while healthy cells, by efficiently converting excess PpIX into heme, do not [2,5]. Under normal circumstances, 5-ALA, because it is not significantly lipid soluble, cannot cross the blood-brain barrier [4].…”

“…Under normal circumstances, 5-ALA, because it is not significantly lipid soluble, cannot cross the blood-brain barrier [4]. However, when the blood-brain barrier is compromised by tumor angiogenesis, 5-ALA is more permeable to the blood-brain barrier, thus contributing to 5-ALA's ability to target tumor tissue [2,4]. In a study by Stummer, et al, the authors found that 5-ALA-induced fluorescence is highly correlated to the magnitude of cell proliferation and cellular density [4].…”

“…In order to evaluate 5-ALA as a viable tool to improve malignant glioma resections, a Phase III randomized clinical trial was conducted in Germany at 15 neurosurgical centers on 322 patients. In this study, patients underwent 5-ALA-induced fluorescence-guided surgery followed by adjuvant radiotherapy or the control protocol, which was radiotherapy after white light neurosurgery [2]. The study concluded that 5-ALA administration significantly increased neurosurgeons' ability to completely remove tumors (total resection in 65% of patients in the 5-ALA arm compared to 36% of patients in the white light arm) and improved progression-free survival after six months (progression-free survival after six months was 41% in the 5-ALA arm compared to 21.1% in the white light arm).…”