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肾癌摄取^(11)C-乙酸的分子机制及相关研究 被引量:2

Mechanism of ^(11)C-acetate uptake in renal cell carcinoma and related experimental research
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摘要 目的 11C-乙酸(11C-AC)PET/CT诊断肾细胞癌的灵敏度高于18F-脱氧葡萄糖(18F-FDG),但其显像机制尚不明确。本研究探讨其被肾细胞癌摄取是否与细胞膜脂肪酸合成相关。方法 1细胞抑制实验:培养3株肾癌细胞(786-0、ACNH和Caki-1),分别以脂肪酸合酶(FAS)抑制剂C75、二甲基亚砜(DMSO)预处理后加入11C-AC,30 min后测细胞摄取放射性计数,并收集细胞提取液测定蛋白浓度,以蛋白免疫印迹检测FAS表达。2小动物PET/CT显像:对786-0荷瘤裸鼠行11C-AC显像,测得肿瘤与软组织的靶本比(T/B),处死裸鼠,取肿瘤组织,免疫组织化学检测FAS表达。结果 786-0细胞株实验组比对照组摄取11C-AC量明显降低,每微克蛋白的放射性摄取值分别为2.430±0.107和3.544±0.443(P=0.013),降低率为31.42%。蛋白免疫印迹实验显示,实验组FAS表达明显低于对照组。ACNH和Caki-1细胞株实验组与对照组每微克蛋白的放射性摄取和FAS表达均无显著差异。小动物PET/CT显示,裸鼠皮下肿瘤11C-AC摄取明显增高,肿瘤免疫组织化学检测FAS表达强阳性。结论肾透明细胞癌原发灶的11C-AC摄取与FAS表达有关,但不同病理类型摄取乙酸的程度不同。 Objective The sensitivity of diagnosing renal cell carcinoma (RCC) by 11C-acetate (11C-AC) PET/CT is higher than 18F-fluorodeoxyglucose (18F-FDG). However, the mechanism of 11C-AC uptake in the tumor is not definite. The present paper aims to identify the correlation between 11C-AC uptake and fatty acid synthesis of cell membrane. Methods In vitro cell uptake and inhibition: 786-0, ACNH and Caki-1 (human renal carcinoma) were cultured, and then treated with C75 (a FAS inhibitor) and dimethyl sulfoxide (DMSO, as control). After 11C-AC was added to cells for 30 min, the lysis extracts were measured in a γ-counter and the protein contents were determined. Then, FAS expression was determined by Western blotting. Micro PET/CT: 786-0-bearing nude mice were scanned by 11C-AC PET/CT and tumor to soft tissue ratios were measured. After imaging, the mice were euthanized, and the tumors were excised for immunohistochemical analysis. Results The 786-0 cells treated with C75 showed inhibition uptake by 31.42% (P=0.013) compared with the control cells. There were no significant differences in 11C-AC uptake between treated cells and control cells for ACNH and Caki-1 cell lines. The visual inspection of the Western blotting results revealed significant differences in band intensity for 786-0 cells, but no differences were found in band intensity for the other two cell lines. The tumors showed significant uptake in micro PET/CT and strong positive in immunohistochemical analysis of FAS expression. Conclusion The 11C-AC uptake in the primary sites of renal clear cell carcinoma was related to the expression of FAS, but different pathological types of renal tumors may utilize acetate through other metabolic pathways.
出处 《肿瘤影像学》 2014年第3期200-204,共5页 Oncoradiology
关键词 11C-乙酸 肾细胞癌 脂肪酸合酶 11C-acetate Renal cell carcinoma Fatty acid synthase
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参考文献7

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二级参考文献15

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