5-氨基乙酰丙酸（5-ALA）荧光引导胶质瘤手术提高了术中肿瘤识别，但肿瘤的侵润边界往往呈现弱荧光，加大了术者对肿瘤边界的识别难度。我们前期研究明确了亚铁螯合酶（FECH）在5-ALA代谢机制过程中的作用，实现了靶向下调FECH表达提高5-ALA荧光成像质量和光动力学效应的目的。有报道表明位于鼠脑脉络丛顶端膜的寡肽转运蛋白 (PEPT2)可将5-ALA从脑脊液转运至血液内，但胶质瘤细胞5-ALA跨膜转运机制不明。本研究拟探索PEPT2在5-ALA转运过程中的作用，检测不同级别胶质瘤组织PEPT2表达，证实其表达和5-ALA荧光激发的关系；探索野生型胶质瘤细胞PEPT2表达和5-ALA荧光强度的潜在关系；靶向干扰PEPT2表达之后，检测5-ALA荧光强度以及胶质瘤细胞生物学行为的改变，并在此基础上探索联合干扰PEPT2和FECH增强5-ALA荧光成像质量和光动力学效应的可行性。

Enhanced 5-ALA-based metabolic imaging and photodynamic therapy efficacy by targeting PEPT2 and FECH..Recurrence of glioma frequently occurs within the marginal area of the surgical cavity due to invading residual cells. 5-aminolevulinic acid (5-ALA) fluorescence-guided resection has been used as effective therapeutic modalities to improve discrimination of brain tumor margins and patient prognosis. However, the marginal areas of glioma usually show vague fluorescence, which makes tumor identification difficult, and the applicability of 5-ALA-based photodynamic therapy (PDT) is hampered by insufficient therapeutic efficacy in glioma tissues. To overcome these issues, we assessed the expression of ferrochelatase (FECH) gene, which encodes a key enzyme that catalyzes the conversion of protoporphyrin IX (PpIX) to heme, in glioma surgical specimens and manipulated FECH in human glioma cell lines. These results suggest that knockdown of FECH is a potential approach to enhancing PpIX fluorescent quality for optimizing the subjective discrimination of vague fluorescence and improving the effect of 5-ALA-PDT..Recently, the report has showed peptide ptransporter 2 (PEPT2)-mediated transport of 5-ALA at the choroid plexus in rat model, however, no data have been indicated concerning the mechanisms of transport of 5-ALA in human gliomas. To understand the mechanisms, whether PEPT2 is present and participates in transport of 5-ALA in gliomas, we focused the PEPT2 in human glioma..The PEPT2 mRNA expression was determined using quantitative RT-PCR (QRT-PCR) in various human astrocytic tumors and normal brain tissue. Cells expressing PEPT2 in normal brain and glioblastoma specimens were identified using immunohistochemistry. PEPT2 transfection with small interference RNA (siRNA）or plasmid were performed to increase intracellular PpIX accumulation in glioma cells. The phototoxicity of ALA-photodynamic therapy (PDT) after transfection with FECH and/or PEPT2 was evaluated by proliferation, invasion, migration assay and cell apoptosis analysis..Our study is manipulated to show the functional characterization of PEPT2 in transport of 5-ALA in gliomas, and enhance 5-ALA-based fluorescent metabolic quality and ALA-PDT efficacy by targeting PEPT2 and FECH.