5-Aminolevulinic Acid (5-ALA)-Induced Protoporphyrin IX Fluorescence by Glioma Cells-A Fluorescence Microscopy Clinical Study

5-氨基乙酰丙酸 (5-ALA) 诱导胶质瘤细胞产生原卟啉 IX 荧光 - 荧光显微镜临床研究

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作者:Simone Pacioni, Quintino Giorgio D'Alessandris, Stefano Giannetti, Giuseppe Maria Della Pepa, Martina Offi, Martina Giordano, Valerio Maria Caccavella, Maria Laura Falchetti, Liverana Lauretti, Roberto Pallini

Abstract

5-aminolevulinic acid (5-ALA)-induced PpIX fluorescence is used by neurosurgeons to identify the tumor cells of high-grade gliomas during operation. However, the issue of whether 5-ALA-induced PpIX fluorescence consistently stains all the tumor cells is still debated. Here, we assessed the cytoplasmatic signal of 5-ALA by fluorescence microscopy in a series of human gliomas. As tumor markers, we used antibodies against collapsin response-mediated protein 5 (CRMP5), alpha thalassemia/mental retardation syndrome X-linked (ATRX), and anti-isocitrate dehydrogenase 1 (IDH1). In grade III-IV gliomas, the signal induced by 5-ALA was detected in 32.7-75.5 percent of CRMP5-expressing tumor cells. In low-grade gliomas (WHO grade II), the CRMP5-expressing tumor cells did not fluoresce following 5-ALA. Immunofluorescence with antibodies that stain various components of the blood-brain barrier (BBB) suggested that 5-ALA does not cross the un-breached BBB, in spite of its small dimension. To conclude, 5-ALA-induced PpIX fluorescence has an established role in high-grade glioma surgery, but it has limited usefulness in surgery for low-grade glioma, especially when the BBB is preserved.

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