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Validation of R-2-[18F]Fluoropropionic Acid as a Potential Tracer for PET Imaging of Liver Cancer

  • Zhanwen Zhang
  • Shaoyu Liu
  • Hui Ma
  • Dahong Nie
  • Fuhua Wen
  • Jing Zhao
  • Aixia Sun
  • Gongjun Yuan
  • Shu Su
  • Xianhong Xiang
  • Ping HuEmail author
  • Ganghua TangEmail author
RESEARCH ARTICLE
  • 42 Downloads

Abstract

Purpose

2-[18F]Fluoropropionic acid (RS-[18F]FPA) has shown potential value as a short-chain fatty acid positron emission tomography (PET) tracer for the detection of liver cancer. However, RS-[18F]FPA is a mixture of 2-R-[18F]fluoropropionic acid (R-[18F]FPA) and 2-S-[18F]fluoropropionic acid (S-[18F]FPA). The aim of this study is to validate the feasibility of R-[18F]FPA in preclinical PET imaging of liver cancer and to compare the use of R-[18F]FPA with that of RS-[18F]FPA and S-[18F]FPA.

Procedures

A comparative study of R-[18F]FPA, RS-[18F]FPA, S-[18F]FPA, and [18F]FDG micro-PET imaging was performed in HepG2 and SK-Hep-1 tumor-bearing mice. A comparison of R-[18F]FPA uptake with that of S-[18F]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-[18F]FPA were comparable to those of RS-[18F]FPA but were higher than those of S-[18F]FPA and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in HepG2 tumors. The radioactivity uptake values of R-[18F]FPA in large HepG2 tumors were lower than those of [18F]FDG (P < 0.05), while R-[18F]FPA PET was significantly superior to [18F]FDG PET in detecting small tumors (both SK-Hep-1 and HepG2 tumors). The in vivo PET imaging experiments showed that R-[18F]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-[18F]FPA in SK-Hep-1 tumor-bearing mice was blocked by 39.5 % with orlistat.

Conclusion

R-[18F]FPA seems to be more potential than S-[18F]FPA as an optically pure PET probe, with effective compensation for the deficiencies of [18F]FDG, particularly in PET imaging of small liver cancer. The uptake mechanism of [18F]FPA in liver cancer may be related to fatty acid synthesis and the tricarboxylic acid cycle. However, compared with the racemic RS-[18F]FPA, the possible advantages of R-enantiomer R-[18F]FPA still needs further research.

Key words

2-[18F]Fluoropropionic acid R,S-enantiomer Liver cancer Positron emission tomography Uptake mechanism 

Notes

Funding information

This study was funded by the National Natural Science Foundation of China (No. 81571704, No. 81371584), the Science and Technology Foundation of Guangdong Province (No. 2016B090920087, No. 2014A020210008), the Science and Technology Planning Project Foundation of Guangzhou (No. 201604020169), and the China Postdoctoral Science Foundation (CPSF) (No.2018M631029 to S Liu).

Compliance with Ethical Standards

The experiments were approved by the Institutional Animal Care and Utilization Committee (IACUU) of the First Affiliated Hospital, Sun Yat-sen University (approval no. 2016058).

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

11307_2019_1346_MOESM1_ESM.pdf (546 kb)
ESM 1 (PDF 546 kb)

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Copyright information

© World Molecular Imaging Society 2019

Authors and Affiliations

  1. 1.Department of Nuclear Medicine and Medical Imaging, Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina
  2. 2.Department of Nuclear Medicine, The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

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