[Intraoperative Fluorescence Imaging of Brain Tumors]

Malignant gliomas are highly invasive tumors. Accurate identification of tumor tissue is essential for enabling tumor resection as much as possible without damaging important neurological functions. One of the methods is intraoperative fluorescence imaging. This method visualizes in real time the boundary between the tumor and normal brain, which cannot be identified using conventional surgical microscope under white light. Although many fluorescent dyes have been reported for intraoperative fluorescence imaging of brain tumors, only 5-aminolevulinic acid(5-ALA)is approved by Ministry of Health, Labour and Welfare in Japan. After the oral administration of 5-ALA, fluorescence is emitted by protoporphyrin Ⅸ, a metabolite of 5-ALA in tumor cells(red fluorescence with a peak at 635 nm, induced by an excitation light of 405 nm). The intensity of fluorescence is correlated with tumor cell density, proliferation rate, and vascular density. In a multicenter randomized controlled study in Germany, compared with white light imaging, fluorescence imaging with 5-ALA increased the tumor resection rate and significantly prolonged progression-free survival at 6 months. However, no difference was observed in overall survival. Regarding other fluorescent substances, fluorescein sodium is a dye that leaks from tumor vessels without the blood-brain barrier, like contrast media used for computed tomography and magnetic resonance imaging(green fluorescence with a peak at 520 nm, induced by an excitation light of 493 nm). This dye spreads in the interstitial tissue of the tumor to visualize the tumor area. Indocyanine green emits a near-infrared light of 820-920 nm, induced by an excitation light of 760- 810 nm. This dye was expected to be useful for visualizing deep tumors as it emits light with high tissue permeability; however, it does not leak out of blood vessels because of its large molecular weight. Subsequently, this dye is used for intraoperative angiography of highly vascularized tumors. Talaporfin sodium was originally developed for photodynamic therapy in Japan and is readily taken up by tumor cells. This substance is also used for intraoperative fluorescence imaging because it emits the fluorescence of 672 nm, induced by an excitation light of 664 nm. Here, we review various fluorescent dyes used for intraoperative imaging of brain tumors.