Department of Nuclear Medicine and Medical Imaging, Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Department of Nuclear Medicine, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
Mol Imaging Biol. 2019 Dec;21(6):1127-1137. doi: 10.1007/s11307-019-01346-1.
2-[F]Fluoropropionic acid (RS-[F]FPA) has shown potential value as a short-chain fatty acid positron emission tomography (PET) tracer for the detection of liver cancer. However, RS-[F]FPA is a mixture of 2-R-[F]fluoropropionic acid (R-[F]FPA) and 2-S-[F]fluoropropionic acid (S-[F]FPA). The aim of this study is to validate the feasibility of R-[F]FPA in preclinical PET imaging of liver cancer and to compare the use of R-[F]FPA with that of RS-[F]FPA and S-[F]FPA.
A comparative study of R-[F]FPA, RS-[F]FPA, S-[F]FPA, and [F]FDG micro-PET imaging was performed in HepG2 and SK-Hep-1 tumor-bearing mice. A comparison of R-[F]FPA uptake with that of S-[F]FPA by HepG2 and SK-Hep-1 cells was made at different time points. Additionally, in vivo blocking experiments in HepG2 and SK-Hep-1 tumor models were conducted with orlistat and 3-nitropropionic acid (3-NP). In vitro blocking experiments with orlistat or 3-NP were performed with HepG2 and SK-Hep-1 cells.
The radioactivity uptake values of R-[F]FPA were comparable to those of RS-[F]FPA but were higher than those of S-[F]FPA and 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) in HepG2 tumors. The radioactivity uptake values of R-[F]FPA in large HepG2 tumors were lower than those of [F]FDG (P < 0.05), while R-[F]FPA PET was significantly superior to [F]FDG PET in detecting small tumors (both SK-Hep-1 and HepG2 tumors). The in vivo PET imaging experiments showed that R-[F]FPA uptake in HepG2 tumor-bearing mice was blocked by 19.3 % and 31.8 % after treatment with orlistat and 3-NP, respectively. The radioactivity uptake values of R-[F]FPA in SK-Hep-1 tumor-bearing mice was blocked by 39.5 % with orlistat.
R-[F]FPA seems to be more potential than S-[F]FPA as an optically pure PET probe, with effective compensation for the deficiencies of [F]FDG, particularly in PET imaging of small liver cancer. The uptake mechanism of [F]FPA in liver cancer may be related to fatty acid synthesis and the tricarboxylic acid cycle. However, compared with the racemic RS-[F]FPA, the possible advantages of R-enantiomer R-[F]FPA still needs further research.
2-[F]氟丙酸（RS-[F]FPA）已显示出作为短链脂肪酸正电子发射断层扫描（PET）示踪剂用于检测肝癌的潜在价值。然而，RS-[F]FPA 是 2-R-[F]氟丙酸（R-[F]FPA）和 2-S-[F]氟丙酸（S-[F]FPA）的混合物。本研究旨在验证 R-[F]FPA 在肝癌临床前 PET 成像中的可行性，并比较 R-[F]FPA 与 RS-[F]FPA 和 S-[F]FPA 的应用。
在 HepG2 和 SK-Hep-1 荷瘤小鼠中进行了 R-[F]FPA、RS-[F]FPA、S-[F]FPA 和 [F]FDG 微 PET 成像的比较研究。在不同时间点比较了 HepG2 和 SK-Hep-1 细胞中 R-[F]FPA 与 S-[F]FPA 的摄取情况。此外，还在 HepG2 和 SK-Hep-1 肿瘤模型中进行了奥利司他和 3-硝基丙酸（3-NP）的体内阻断实验。在 HepG2 和 SK-Hep-1 细胞中进行了奥利司他或 3-NP 的体外阻断实验。
R-[F]FPA 的放射性摄取值与 RS-[F]FPA 相当，但高于 S-[F]FPA 和 2-脱氧-2-[F]氟-D-葡萄糖 ([F]FDG) 在 HepG2 肿瘤中的摄取值。在较大的 HepG2 肿瘤中，R-[F]FPA 的放射性摄取值低于 [F]FDG（P<0.05），而 R-[F]FPA PET 在检测小肿瘤（SK-Hep-1 和 HepG2 肿瘤）方面明显优于 [F]FDG PET。体内 PET 成像实验表明，奥利司他和 3-NP 处理后，HepG2 荷瘤小鼠中 R-[F]FPA 的摄取分别被阻断了 19.3%和 31.8%。奥利司他处理后，SK-Hep-1 荷瘤小鼠中 R-[F]FPA 的放射性摄取值被阻断了 39.5%。
R-[F]FPA 似乎比 S-[F]FPA 更有潜力作为一种光学纯的 PET 探针，有效弥补了 [F]FDG 的不足，特别是在小肝癌的 PET 成像中。肝癌中 [F]FPA 的摄取机制可能与脂肪酸合成和三羧酸循环有关。然而，与外消旋 RS-[F]FPA 相比，R-[F]FPA 的可能优势仍需要进一步研究。
