[1]赵竞,张占文,马慧,等.PET/CT显像剂18F-氟丙酸在肝癌中的生物学评估[J].国际放射医学核医学杂志,2018,(5):414-419.[doi:10.3760/cma.j.issn.1673-4114.2018.05.005]
　Zhao Jing,Zhang Zhanwen,Ma Hui,et al.Biological evaluation of PET/CT imaging agent 18F-fluoropropionic acid in hepatocellular carcinoma[J].International Journal of Radiation Medicine and Nuclear Medicine,2018,(5):414-419.[doi:10.3760/cma.j.issn.1673-4114.2018.05.005]
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《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
期数:
2018年第5期
页码:
414-419
栏目:
基础研究
出版日期:
2018-10-01

文章信息/Info

Title:
Biological evaluation of PET/CT imaging agent 18F-fluoropropionic acid in hepatocellular carcinoma
作者:
赵竞1;  张占文2;  马慧3;  聂大红4;  蒋宁一1;  刘生1;  唐刚华3
1. 510120 广州, 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;
2. 510655 广州, 中山大学附属第六医院核医学科;
3. 510080 广州, 中山大学附属第一医院核医学科;
4. 510080 广州, 中山大学附属第一医院放疗科
Author(s):
Zhao Jing1;  Zhang Zhanwen2;  Ma Hui3;  Nie Dahong4;  Jiang Ningyi1;  Liu Sheng1;  Tang Ganghua3
1. 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;
2. Department of Nuclear Medicine, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China;
3. Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;
4. Department of Radiation Oncology, The First Affiliated Hospital, SunYat-sen University, Guangzhou 510080, China
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
Keywords:
Carcinoma;  hepatocellular;  Positron emission tomography computed tomography;  18F-fluoropropionic acid
DOI:
10.3760/cma.j.issn.1673-4114.2018.05.005
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。
Abstract:
Objective To evaluate the potential of 18F-fluoropropionic 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, 18F-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.

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备注/Memo

备注/Memo:
收稿日期:2018-05-23。
基金项目:国家自然科学基金（81671719、81571704）；广东省科技计划基金（2016B090920087、2013B021800264）；广州市科技计划基金（201604020169、201510010145）
通讯作者:刘生,Email:liusheng_gz@126.com;唐刚华,Email:gtang0224@126.com
更新日期/Last Update: 2018-10-01