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

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.