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_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 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