PET／CT显像剂^18F-氟丙酸在肝癌中的生物学评估  

Biological evaluation of PET/CT imaging agent ^18F-fluoropropionic acid in hepatocellular carcinoma

作　　者：赵竞[1] 张占文[2] 马慧 聂大红[4] 蒋宁一[1] 刘生[1] 唐刚华[3] Zhao Jing;Zhang Zhanwen;Ma Hui;Nie Dahong;Jiang Ningyi;Liu Sheng;Tang Ganghua(Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation/Department of Nuclear Medicine,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China;Department of Nuclear Medicine,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou 510655,Chin;Department of Nuclear Medicine,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,Chin;Department of Radiation Oncology,The First Affiliated Hospital,SunYat-sen University,Guangzhou 510080,China)

机构地区：[1]中山大学孙逸仙纪念医院,广东省恶性肿瘤表观遗传与基因调控重点实验室/核医学科,广州510120 [2]中山大学附属第六医院核医学科,广州510655 [3]中山大学附属第一医院核医学科,广州510080 [4]中山大学附属第一医院放疗科,广州510080

出　　处：《国际放射医学核医学杂志》2018年第5期414-419,共6页International Journal of Radiation Medicine and Nuclear Medicine

基　　金：国家自然科学基金（81671719、81571704）;广东省科技计划基金（20168090920087、20138021800264）;广州市科技计划基金（201604020169、201510010145）

摘　　要：目的 探讨PET/CT显像剂^18F-氟丙酸（18F-FPA）对肝细胞肝癌（HCC）的显像效果及其摄取机制.方法 （1）以甲基-2-溴丙酸乙酯为前体合成18F-FPA;（2）通过体外细胞摄取实验测定人肝癌SK-Hep 1细胞不同时间点对^18F-FpA的放射性摄取情况;观察不同浓度脂肪酸合成酶抑制剂-奥利司他（Orilistat）、乙酰辅酶A羧化酶抑制剂5-十四烷氧基-2-呋喃甲酸（TOFA）对^18F-FPA的摄取抑制情况;（3）对荷人肝癌SK-Hep 1小鼠行^18F-FPA microPET/CT显像,并与^18F-FDG PET/CT显像进行比较.^18F-FPA和^18F-FDG在肿瘤中的放射性摄取率比较采用t检验.结果 （1）^18F-FPA的合成产率为（45±2）％.（2）细胞摄取实验结果显示,人肝癌SK-Hep 1细胞对^18F-FPA的摄取率从5 min的（1.3±0.4）％上升到120 min的（4.6±0.2）％.细胞摄取抑制实验结果显示,随着抑制剂浓度的增高,人肝癌SK-Hep 1细胞对^18F-FPA的摄取逐渐降低.当抑制剂奥利司他和TOFA浓度均为400 μmol时,人肝癌SK-Hep 1细胞对^18F-FPA的摄取率分别降低了（40.3±4.0）％和（26.0±6.0）％.（3）荷人肝癌SK-Hep 1小鼠18F-FPA microPET/CT显像显示了快速且准确的肿瘤定位,肿瘤/肝脏比值为1.63±0.26;^18F-FDG PET/CT显像中的肿瘤/肝脏比值为1.09±0.21.^18F-FPA比^18F-FDG具有更好的显像效果,差异有统计学意义（t=4.055,P=0.047）.结论 ^18F-FPA可用于肝癌显像,且其摄取与脂肪酸合成有关.Objective To evaluate the potential of ^18F-fluoropiopionic acid（18F-FPA）as a PET/CT tracer in the imaging of hepatocellular carcinoma （HCC） and to identify the mechanism underlying ^18F-FPA uptake.Methods （1） ^18F-FPA was synthesized from the precursor methyl-2-bromopropionate.（2） ^18F-FPA uptake by SK-Hep 1 HCC cells was quantified in vitro at different time points.To further investigate the mechanism underlying ^18F-FPA uptake,the inhibitory effects of the fatty acid synthase inhibitor Orilistat and the acetyl-CoA carboxylase inhibitor 5-tetradecyloxy-2-furoic acid on ^18F-FPA uptake were observed.（3） Micro-PET/CT imaging results for ^18F-FPA and ^18F-FDG for mouse models of human hepatocellular carcinoma SK-Hep 1 were obtained and compared.Mthe radioactivity uptake ratios of ^18F-FDA and ^18F-FDG were compared and analyzed with t test.Results （1） ^18F-FPA was synthesized with a yield of 45±2% through a simple process.（2） ^18F-FPA uptake ratio by SK-Hep 1 cells gradually increased from（1.3±0.4）% after 5 min to （4.6 ± 0.2）% after 120 min.In the cell uptake inhibition experiments,^18F-FPA uptake by SK-Hep 1 cells gradually decreased as inhibitor concentration increased.Under Orilistat and TOFA concentrations of 400 μmol,IF-FPA uptake by SK-Hep 1 cells decreased by （40.3±4.0）% and （26.0±6.0）%,respectively.（3）^18F-FPA showed rapid and accurate tumor localization in mouse models of human hepatocellular carcinoma SK-Hep 1 with a tumor/liver ratio of 1.63±0.26.When used in ^18F-FDG PET/CT imaging,the tumor/liver ratio of ^18F-FPA reached 1.09±0.21.The imaging results provided by ^18F-FPA were superior to those provided by ^18F-FDG （t=4.055,P=0.047）.Conclusion ^18F-FPA can be used as an alternative radiotracer in the detection of hepatocellular carcinoma,its uptake is related to fatty acid synthesis.

关 键 词：癌 肝细胞 正电子发射断层显像计算机体层摄影术 ^18F-氟丙酸 

分 类 号：R735.7[医药卫生—肿瘤]