• Xiaofeng Chen, Chunlei Wang, Lei Teng, Yaohua Liu, Xin Chen, Guang Yang, Ligang Wang, Huailei Liu, Ziyi Liu, Dongzhi Zhang, Yongxiang Zhang, Hongpeng Guan, Xianfeng Li, Changyu Fu, Boxian Zhao, Fei Yin, and Shiguang Zhao.
• Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University , Harbin , People's Republic of China.
• Acta Oncol. 2014 Mar 1;53(3):405-13.

BackgroundGlioma recurrence frequently occurs close to the marginal area of the surgical cavity as a result of residual infiltrating glioma cells. Fluorescence-guided surgery with 5-aminolevulinic acid (ALA) for resection of gliomas has been used as an effective therapeutic approach to discriminate malignant tissue from brain tissue and to facilitate patient prognosis. ALA-based photodynamic therapy is an effective adjuvant treatment modality for gliomas. However, insufficient protoporphyrin IX (PpIX) accumulation may limit the applicability of fluorescence-guided resection and photodynamic therapy in the marginal areas of gliomas.MethodsTo be able to understand how to overcome these issues, human glioma cells and normal astrocytes were used as the model system. Glioma cells and astrocytes were preconditioned with calcitriol for 48 hours and then incubated with ALA. Changes in ALA-induced PpIX fluorescence and cell survival after light exposure were assessed. Furthermore, expression of porphyrin synthetic enzymes in pretreated glioma cells was analyzed.ResultsCalcitriol can be administered prior to ALA as a non-toxic preconditioning regimen to significantly enhance ALA-induced PpIX levels and fluorescence. This increase in PpIX level was detected preferentially in glioma versus normal cells. Also, calcitriol pretreated glioma cells exhibited increased cell death following ALA-based photodynamic therapy. Furthermore, mechanistic studies documented that expression of the porphyrin synthesis enzymes coproporphyrinogen oxidase was increased by calcitriol at the mRNA level.ConclusionWe demonstrated for the first time a simple, non-toxic and highly effective preconditioning regimen to selectively enhance PpIX fluorescence and the response of ALA-PDT in glioma cells. This finding suggests that the combined treatment of glioma cells with calcitriol plus ALA may provide an effective and selective therapeutic modality to enhance ALA-induced PpIX fluorescent quality for improving discrimination of tumor tissue and PDT efficacy.

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