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

孙玉云; 张　健; 郑营营

doi:10.19401/j.cnki.1007-3639.2018.05.002

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

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- Evaluating the change of fatty acid synthesis in renal cell carcinoma by 18F-FAC microPET/CT imaging
- China Oncology Vol. 28, Issue 5, Pages: 327-334(2018)
- 作者机构：
  
  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
  2. 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
  3. 复旦大学核物理与离子束应用教育部重点实验室,上海,200433
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2018.05.002
  CLC： R737.11
- Published Online：12 June 2018，
  
  Published：12 June 2018
- 稿件说明：
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孙玉云,张　健,郑营营,等.

孙玉云, 张　健, 郑营营. Evaluating the change of fatty acid synthesis in renal cell carcinoma by 18F-FAC microPET/CT imaging[J]. China Oncology, 2018, 28(5): 327-334.
孙玉云,张　健,郑营营,等. DOI： 10.19401/j.cnki.1007-3639.2018.05.002.

孙玉云, 张　健, 郑营营. Evaluating the change of fatty acid synthesis in renal cell carcinoma by 18F-FAC microPET/CT imaging[J]. China Oncology, 2018, 28(5): 327-334. DOI： 10.19401/j.cnki.1007-3639.2018.05.002.

摘要

背景与目的：由于肾细胞癌脂肪酸代谢异常升高，

C-乙酸（

C-acetate，

C-AC）PET/CT显像已用于诊断肾细胞癌，能弥补

F-FDG PET/CT显像在肾癌诊断方面的不足。然而，

C的半衰期很短（t

1/2

=20.4 min），极大地限制了

C-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

F-氟乙酸盐（

F-fluoroacetate，

F-FAC）与脂肪酸合成酶（fatty acid synthase，FAS）的相关性，进而探讨

F-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

F-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

F-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

F-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

F-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。

F-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，

F-FAC摄取与FAS表达具有良好的正向相关性（P0.001）。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，P0.01）。结论：肾癌摄取

F-FAC与FAS表达具有良好的相关性，可以利用

F-FAC PET/CT实现在体监测肾癌脂肪酸代谢的动态变化。

Abstract

Background and purpose: Increased fatty acid biosynthesis is one of the main characteristics in renal cell carcinoma (RCC).

C-acetate (

C-AC) PET/CT imaging has been used to diagnose RCC. It can provide more diagnostic benefits than

F-FDG PET/CT. However

C-AC PET/CT imaging has some limitations such as the short half-life of

C (t

1/2

=20.4 min)

which limits the widespread use of

C-AC. The main purpose of our study was to investigate the relationship between the uptake of

F-fluoroacetate (

F-FAC) and the expression of fatty acid synthase (FAS) and whether

F-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

F-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.

F-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

max

of the tumor to the %ID/g

max

of 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

F-FAC was 8.087±0.792

9.708±0.792

10.285±0.751

and 10.859±1.100 at day 0

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

F-FAC in both groups increased. However

it was significantly lower in everolimus group than that in the control group. The change of

F-FAC T/M and FAS expression were consistent with the uptake of

F-FAC

and the correlation analysis showed that the

F-FAC uptake was positively correlated with the FAS expression (P0.001). Finally

mice in everolimus group had smaller tumor volume and longer median survival time (35 d vs 23 d

P0.01) than the mice in control group. Conclusion: We successfully found a significant correlation between the uptake of

F-FAC and the expression of FAS and we can monitor the changes of fatty acid synthesis in RCC by

F-FAC PET/CT molecular imaging.

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