靶向肿瘤代谢异常是肿瘤治疗的一个重要策略。18F-FDG PET/CT可以监测结直肠癌葡萄糖代谢水平以判断疗效和预后。申请人前期发现，蛋白质翻译后修饰酶SIRT5在结直肠癌组织中表达增高，SIRT5的高表达导致患者的不良预后；同时SIRT5可以促进结直肠癌细胞18F-FDG摄取和生长，这可能与SIRT5结合并去酰化修饰糖酵解关键酶LDHA进而导致AKT磷酸化密切相关。本项目将通过体内和体外实验揭示SIRT5与结直肠癌糖酵解水平的关系及机制，尤其是SIRT5通过LHDA去酰化修饰调节AKT磷酸化水平的具体分子机制及意义。同时评估通过18F-FDG以及18F-SDF-1α PET监测SIRT5抑制剂治疗结直肠癌的可行性。本研究将构建SIRT5靶向治疗分子影像诊疗体系，这对推动SIRT5靶向结直肠癌葡萄糖代谢治疗走向临床提供可视化、无创性、动态疗效监测和预后评估手段具有极其重要意义。

Targeting metabolic pathway is an important strategy for tumor treatment. 18F-FDG PET/CT can monitor glucose metabolism in colorectal cancer (CRC) to determine efficacy and prognosis of CRC treatment. Our previous study indicated that, as a protein post-translational modification enzyme, SIRT5 was highly expressed in CRC tissues. Furthermore, patients expressing high levels of SIRT5 exhibited unfavorable outcomes for both overall survival rate and disease-free survival rate. The following study found that SIRT5 significantly promoted 18F-FDG uptake and cell growth. SIRT5 might combine with glycolytic key enzyme LDHA and regulate LDHA lysine acylation level by post-translational modification which leads to the activation of pAKT pathway. This study will investigate the relationship between SIRT5, 18F-FDG uptake and cell growth in vivo and vitro, and the role of LDHA post-translation modification mediated pAKT in regulating 18F-FDG uptake. We will also assess the effectiveness of 18F-FDG & 18F-SDF-1α PET in monitoring the response of SIRT5-targeted therapy. This study will establish a molecular imaging protocol for SIRT5-targeted therapy in CRC, and develop a visualized, living, non-invasive, and dynamic method to make accurate prognostic evaluation for SIRT5-targeted therapy, which will hopefully push SIRT5 inhibitor treatment to the clinical use in the future.