R-2-[F]氟丙酸作为肝癌正电子发射断层成像潜在示踪剂的验证。
Validation of R-2-[F]Fluoropropionic Acid as a Potential Tracer for PET Imaging of Liver Cancer.
机构信息
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.
出版信息
Mol Imaging Biol. 2019 Dec;21(6):1127-1137. doi: 10.1007/s11307-019-01346-1.
PURPOSE
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.
PROCEDURES
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.
RESULTS
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.
CONCLUSION
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.
目的
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。
方法
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。
结果
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%。
结论
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。
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