Issue (if applicable)
Glioblastoma multiforme (GBM) is a devastating form of cancer, and essentially all GBM tumors recur causing fatality. A new surgical technique, fluorescence-guided resection of GBM using 5-aminolevulinic acid (5-ala), improves the extent of resection and positively impacts the length and quality of patient survival. The fluorescence achieved in neoplastic tissue depends directly on the accumulation of porphyrins derived from the metabolism of the 5-ala prodrug within the cancer cell. However, 5-ala induced fluorescence has been reported to be inconsistent. In an effort to determine the cause of the inconsistent fluorescence, the authors investigated the effect of medications commonly prescribed to brain tumor patients on 5-ala induced fluorescence. A model was developed to quantify intracellular porphyrin accumulation using a U87MG GBM cell line constitutively expressing yellow fluorescent protein (YFP-U87). 5-ala mediated fluorescence within the cells was standardized to cell number via the fluorescence emission spectra ratio of porphyrin (405 nm) to YFP (525 nm). 5-ala induced accumulation of porphyrins was measured after treating YFP-U87 cells with phenytoin, dexamethasone, or desipramine for 3 days. After a 6 hour incubation with 5-ala, no significant difference in porphyrin accumulation was observed in cells treated with dexamethasone or desipramine. Phenytoin, however, significantly reduced the accumulation of fluorescent porphyrins within the YFP-U87 cell line by nearly 30% compared to the control. To optimize fluorescence during surgery and improve patient survival these results suggest that further investigations are warranted to determine the effects of commonly administered medications on 5-ala fluorescence-guided resection of GBM.
Christopher Steele, Johnathan E. Lawrence, Richard A. Rovin, and Robert J. Winn. "Phenytoin reduces 5-ala mediated fluorescence in glioblastoma cells" Neuro-Oncology 15.suppl 3 (2013): iii217-iii225. Available at: http://works.bepress.com/johnathan_lawrence/2