PET/CT显像剂[18F]-AIF-NOTA-NSC-GLU在荷HepG2肝癌模型中的生物学评估  

Biological evaluation of [18F]-AIF-NOTA-NSC-GLU as a PET/CT tracer for human HepG2 Hepatoma

作　　者：林丽萍[1] 唐刚华[2] 聂大红[3] 苏舒[1] 熊鹦 刘少玉[2] 马慧 元龚骏[2] 向贤宏[1] LIN Liping;TANG Ganghua;NIE Dahong;SU Shu;XIONG Ying;LIU Shaoyu;MA Hui;YUAN Gongjun;XIANG Xianhong(Department of Imaging and Nuclear Medicine,the First Affiliated Hospital of Sun Yat.sen University,Guangzhou 510055,China)

机构地区：[1]中山大学附属第一医院放射介入科,广州510055 [2]中山大学附属第一医院核医学科,广州510055 [3]中山大学附属第一医院放射治疗科,广州510055 [4]中山大学孙逸仙纪念医院,广州510080

出　　处：《实用医学杂志》2019年第18期2868-2873,共6页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:81671719,81571704)

摘　　要：目的合成PET/CT显像剂[18F]-AIF-NOTA-NSC-GLU以及探讨其对荷HepG2肝癌模型的显像效果。方法(1)合成[18F]-AIF-NOTA-NSC-GLU;(2)选用人源性HepG2肝癌细胞株进行[18F]-AIF-NOTA-NSC-GLU体外细胞摄取实验、氨基酸转运竞争抑制实验以及蛋白参与实验;(3)建立荷HepG2肝癌模型并进行[18F]-AIF-NOTA-NSC-GLU显像,与[18F]-氟代脱氧葡萄糖([18F]-FDG)PET/CT进行对比研究,评价[18F]-AIF-NOTA-NSC-GLU对肝癌的显像效果。结果(1)[18F]-AIF-NOTA-NSC-GLU未经衰减校正的合成产率为(29.3±4.6)%(n=10);(2)细胞摄取实验结果显示,人肝癌HepG2细胞对[18F]-AIF-NOTA-NSC-GLU的摄取在30 min达到峰值(7.2±0.37)%;[18F]-AIF-NOTA-NSC-GLU的主要通过氨基酸转运Na+依赖型XAG-系统,Na+依赖型ASC系统和B0+系统部分参与[18F]-AIF-NOTA-NSC-GLU的摄取,几乎不参与蛋白合成;(3)注射[18F]-AIF-NOTA-NSC-GLU 30 min后肿瘤显影清晰,[18F]-AIF-NOTA-NSC-GLU肿瘤/肝比值稍高于60 min[18F]-FDG肿瘤/肝比值[(1.50±0.10)vs.(1.12±0.15),n=3,P=0.023]。结论[18F]-AIFN-OTA-NSC-GLU易于合成,可用于肝癌显像。Objective The aim of this work is to explore the synthesis of imaging agent[18F]-AIF-NOTA-NSC-GLU and its imaging potential in nude mice bearing human HepG2 hepatoma. Methods 1)[18F]-AIF-NOTA-NSC-GLU was synthesized.(2)In vitro competitive inhibition and protein incorporation experiments of[18F]-AIF-NOTA-NSC-GLU were performed with human HepG2 cell lines;(3)The HepG2 hepatoma cancer-bearing nude mice models were constructed. Small-animal PET/CT imaging using[18F]-AIF-NOTA-NSC-GLU was conducted in these models,which were compared with those by 2-deoxy-2-18F fluoro-D-glueose([18F]-FDG)in order to evaluate the imaging value of[18F]-AIF-NOTA-NSC-GLU in hepatoma. Results(1)The overall radiochemical yield of[18F]-AIF-NOTA-NSC-GLU from[18F]was(29.3 ± 4.6)%(n = 10)without decay correction.(2)The cell uptake resulted exhibited the highest uptake of[18F]-AIF-NOTA-NSC-GLU in HepG2 cell was(7.2 ± 0.37)% at 30 min.[18F]-AIF-NOTA-NSC-GLU was primarily transported through Na+-dependent system XAG-,Na+dependent system ASC and system B0+were partly involved in the uptake of[18F]-AIF-NOTA-NSC-GLU,and was not incorporated into protein.(3)The tumor image in hepatic cancer-bearing nude mice was developed clearly at 30 min post-injection. The uptake ratio of tumor to liver tissue for[18F]-AIF-NOTA-NSC-GLU was slightly higher than that of[18F]-FDG at 60 min post-injection[(1.50 ± 0.10)vs.(1.12 ± 0.15),n = 3,P < 0.05]. Conclusion [18F]-AIF-NOTA-NSC-GLU is efficiently prepared and can be used as an alternative agent in the hepatocellular carcinoma imaging.

关 键 词：肝癌 诊断 正电子发射计算机断层显像 [18F]-氟代脱氧葡萄糖 [18F]-AIF-NOTA-NSC-GLU 

分 类 号：R730.44[医药卫生—肿瘤] R735.7[医药卫生—临床医学]