title: Simple and rapid radiosynthesis of N-18F-labeled glutamic acid as a hepatocellular carcinoma PET tracer.
abstract: BACKGROUND
  We have reported that N-(2-18F-fluoropropionyl)-L-glutamate (18F-FPGLU) showed good tumor-to-background contrast and18F-FPGLU was prepared via complex multi-step reaction sequence; here, it is synthesized by a facile two-step reaction sequence. The objectives of this study are to synthesize18F-FPGLU via a two-step reaction sequence and to evaluate the value of18F-FPGLU in nude mice bearing human hepatocellular carcinoma SMCC-7721 (HCC SMCC-7721).
  
  
  METHODS
  18F-FPGLU was synthetized from the precursor (2S)-dimethyl 2-(2-bromopropanamido)pentanedioate via the two-step on-column hydrolysis using a modified commercial FDG synthesizer. To investigate the transport mechanism of18F-FPGLU, we conducted a series of competitive inhibition experiments on HCC SMCC-7721 cells in the absence or presence of Na+and various types of inhibitors. Small-animal PET-CT imaging was performed on tumor-bearing nude mice using18F-FPGLU and 2-18F-2-deoxy-D-glucose (18F-FDG).
  
  
  RESULTS
  The radiochemical yield of18F-FPGLU was up to 15±5% (EOS, n=10) in 35min with the two-step procedure and the radiochemical purity was higher than 95% with a specific activity of 30-40GBq/μmol. In vitro cell experiments show that18F-FPGLU is primarily transported through the Na+-dependent system XAG- and Na+-independent system XC-. PET imaging in a tumor model indicates that18F-FPGLU may be superior to18F-FDG for hepatocellular carcinoma (HCC) imaging.
  
  
  CONCLUSIONS
  An optimized route to prepare18F-FPGLU was developed and18F-FPGLU was synthetized from the precursor ((2S)-dimethyl 2-(2-bromopropanamido)pentanedioate) via the two-step on-column hydrolysis.18F-FPGLU was a potential novel PET tracer for HCC imaging.
authors.affiliation: Department of Nuclear Medicine, Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Aixia
authors.initials: A
authors.lastname: Sun
authors.affiliation: Department of Nuclear Medicine, Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Shaoyu
authors.initials: S
authors.lastname: Liu
authors.affiliation: School of Materials and Energy, South China Agricultural University, Guangzhou 510642, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Nuclear Medicine, Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Dahong
authors.initials: D
authors.lastname: Nie
authors.affiliation: Department of Nuclear Medicine, Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China. Electronic address: gtang0224@126.com.
authors.forename: Ganghua
authors.initials: G
authors.lastname: Tang
authors.affiliation: Department of Nuclear Medicine, Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Zhanwen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Fuhua
authors.initials: F
authors.lastname: Wen
authors.affiliation: Department of Nuclear Medicine, Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D060326:Chemistry Techniques, Synthetic; D005462:Fluorine Radioisotopes; D018698:Glutamic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D007553:Isotope Labeling; D007700:Kinetics; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography / Q000379:methods*; D011849:Radioactive Tracers; D011854:Radiochemistry; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D011849:Radioactive Tracers; D018698:Glutamic Acid
keywords: Amino acid transport; Hepatocellular carcinoma; N-(2-(18)F-fluoropropionyl)-L-glutamate; Positron emission tomography (PET)