18F-FAC PET/CT在体监测肾癌脂肪酸代谢动态变化

doi:10.19401/j.cnki.1007-3639.2018.05.002

中国癌症杂志 ›› 2018, Vol. 28 ›› Issue (5): 327-334.doi: 10.19401/j.cnki.1007-3639.2018.05.002

¹⁸F-FAC PET/CT在体监测肾癌脂肪酸代谢动态变化

孙玉云^1,2，张　健^1,3，郑营营^1,2，顾丙新^1,2，罗建民^1,2，张建平^1,2，徐俊彦^1,2，章英剑^1,2，王明伟^1,2

1. 复旦大学附属肿瘤医院核医学科，复旦大学上海医学院肿瘤学系，复旦大学生物医学
影像研究中心，上海分子影像探针工程技术研究中心，上海 200032 ；
2. 复旦大学核物理与离子束应用教育部重点实验室，上海 200433 ；
3. 上海师范大学生命与环境科学学院，上海 200234

出版日期:2018-05-30 发布日期:2018-06-12
通信作者: 王明伟 E-mail: wangmw@shca.org.cn
基金资助:
国家自然科学基金（21771041，11275050）。

Evaluating the change of fatty acid synthesis in renal cell carcinoma by 18F-FAC microPET/CT imaging

SUN Yuyun^1,2, ZHANG Jian^1,3, ZHENG Yingying^1,2, GU Bingxin^1,2, LUO Jianmin^1,2, ZHANG Jianping^1,2, XU Junyan^1,2, ZHANG Yingjian^1,2, WANG Mingwei^1,2

1.Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Center for Molecular Imaging, Fudan University, Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China; 2. Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai 200433, China; 3. College of Life and Environmental Sciences, Shanghai Normal University, Shanghai 200234, China

Published:2018-05-30 Online:2018-06-12
Contact: WANG Mingwei E-mail: wangmw@shca.org.cn

摘要/Abstract

摘要： 背景与目的：由于肾细胞癌脂肪酸代谢异常升高，¹¹C-乙酸（¹¹C-acetate，¹¹C-AC）PET/CT显像已用于诊断肾细胞癌，能弥补¹⁸F-FDG PET/CT显像在肾癌诊断方面的不足。然而，¹¹C的半衰期很短（t_1/2=20.4 min），极大地限制了¹¹C-AC PET/CT显像在临床诊断中的广泛应用。本实验旨在研究肾癌摄取¹⁸F-氟乙酸盐（¹⁸F-fluoroacetate，¹⁸F-FAC）与脂肪酸合成酶（fatty acid synthase，FAS）的相关性，进而探讨¹⁸F-FAC PET/CT分子影像是否能在体监测肾癌脂肪酸代谢的动态变化。方法：50只ACHN肾癌荷瘤裸小鼠分为3组，分别为¹⁸F-FAC microPET/CT显像组（n=6）、免疫组织化学组（n=24）和生存期观察组（n=20）。其中每组又分为2个亚组，即实验组（10 mg/kg，依维莫司）和对照组（0.9%NaCl溶液），连续处理14 d。在处理前（第0天）和处理后第5、10和15天行小动物¹⁸F-FAC PET/CT显像，定量分析肿瘤与对侧大腿肌肉每克组织放射性占注射量的百分比最大值（the maximum of the percent injected dose per gram tissue，%ID/g_max），并计算靶本比（T/M）。在上述相同时间点，分别随机处死3只荷瘤裸鼠，获取肿瘤组织，进行FAS免疫组织化学染色，并定量计算FAS表达水平。实验期间，每隔1天测量并记录荷瘤鼠肿瘤体积大小，观察荷瘤鼠死亡时间并绘制生存期曲线。结果：根据¹⁸F-FAC PET/CT显像和定量分析，在第0、5、10和15天时实验组肾癌组织的¹⁸F-FAC摄取值%ID/g_max分别为8.087±0.792、9.708±0.792、10.285±0.751和10.859±1.100，对照组分别为8.425±0.549、10.560±0.677、12.325±0.275和13.450±0.517，均有动态增加的变化趋势，但实验组明显低于对照组，并且差异有统计学意义。¹⁸F-FAC T/M和FAS表达也有类似的动态变化，而且相关性分析发现，¹⁸F-FAC摄取与FAS表达具有良好的正向相关性（P<0.001）。肿瘤体积变化和生存期实验表明，实验组肿瘤体积生长明显缓慢，荷瘤鼠中位生存期明显延长（35 d vs 23 d，P<0.01）。结论：肾癌摄取¹⁸F-FAC与FAS表达具有良好的相关性，可以利用¹⁸F-FAC PET/CT实现在体监测肾癌脂肪酸代谢的动态变化。

关键词: ¹⁸F-乙酸, PET/CT, 脂肪酸合成酶, 肾细胞癌

Abstract: Background and purpose: Increased fatty acid biosynthesis is one of the main characteristics in renal cell carcinoma (RCC). ¹¹C-acetate (¹¹C-AC) PET/CT imaging has been used to diagnose RCC. It can provide more diagnostic benefits than ¹⁸F-FDG PET/CT. However, ¹¹C-AC PET/CT imaging has some limitations such as the short half-life of ¹¹C (t_1/2=20.4 min), which limits the widespread use of ¹¹C-AC. The main purpose of our study was to investigate the relationship between the uptake of ¹⁸F-fluoroacetate (¹⁸F-FAC) and the expression of fatty acid synthase (FAS) and whether ¹⁸F-FAC PET/CT imaging can evaluate the change of fatty acid biosynthesis in RCC. Methods: Fifty ACHN tumor-bearing mice were arbitrarily divided into three groups: mice for ¹⁸F-FAC microPET/CT imaging (n=6), FAS immunohistochemical (IHC) staining (n=24), and survival analysis (n=20), respectively. Each group was divided into two subgroups: the everolimus treatment group (10 mg/kg) and the control group (saline), both groups were treated for 14 d. ¹⁸F-FAC microPET/CT was performed before treatment (day 0) and at day 5, 10 and 15 after treatment. The maximum of the percent injected dose per gram tissue (%ID/g_max) of tumor and the ratio of the %ID/g_maxof the tumor to the %ID/g_maxof contralateral thigh muscle (T/M) were quantitatively calculated. Three tumor-bearing mice were randomly sacrificed to obtain tumor tissue and then to carry out FAS IHC staining. The expression of FAS was quantitatively calculated. Tumor sizes and survival were recorded every other day. Results: The uptake of ¹⁸F-FAC was 8.087±0.792, 9.708±0.792, 10.285±0.751, and 10.859±1.100 at day 0, 5, 10, and 15 after treatment in everolimus group, and 8.425±0.549, 10.560±0.677, 12.325±0.275 and 13.450±0.517 in the control group, respectively. Moreover, the uptake of ¹⁸F-FAC in both groups increased. However, it was significantly lower in everolimus group than that in the control group. The change of ¹⁸F-FAC T/M and FAS expression were consistent with the uptake of ¹⁸F-FAC, and the correlation analysis showed that the ¹⁸F-FAC uptake was positively correlated with the FAS expression (P<0.001). Finally, mice in everolimus group had smaller tumor volume and longer median survival time (35 d vs 23 d, P<0.01) than the mice in control group. Conclusion: We successfully found a significant correlation between the uptake of ¹⁸F-FAC and the expression of FAS and we can monitor the changes of fatty acid synthesis in RCC by ¹⁸F-FAC PET/CT molecular imaging.

Key words: ¹⁸F-fluoroacetate, PET/CT, Fatty acid synthase, Renal cell carcinoma

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¹⁸F-FAC PET/CT在体监测肾癌脂肪酸代谢动态变化

Evaluating the change of fatty acid synthesis in renal cell carcinoma by 18F-FAC microPET/CT imaging

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