title: Radiosynthesis and biological evaluation of 5-(3-[18F]fluoropropyloxy)-L-tryptophan for tumor PET imaging.
abstract: BACKGROUND
  [(18)F]FDG PET has difficulty distinguishing tumor from inflammation in the clinic because of the same high uptake in nonmalignant and inflammatory tissue. In contrast, amino acid tracers do not accumulate in inflamed tissues and thus provide an excellent opportunity for their use in clinical cancer imaging. In this study, we developed a new amino acid tracer 5-(3-[(18)F]Fluoropropyloxy)-L-tryptophan ([(18)F]-L-FPTP) by two-step reactions and performed its biologic evaluation.
  
  
  METHODS
  [(18)F]-L-FPTP was prepared by [(18)F]fluoropropylation of 5-hydroxy-L-tryptophan disodium salt and purification on C18 cartridges. The biodistribution of [(18)F]-L-FPTP was determined in normal mice and the incorporation of [(18)F]-L-FPTP into tissue proteins was investigated. In vitro competitive inhibition experiments were performed with Hepa1-6 hepatoma cell lines. [(18)F]-L-FPTP PET imaging was performed on tumor-bearing and inflammation mice and compared with [(18)F]-L-FEHTP PET.
  
  
  RESULTS
  The overall uncorrected radiochemical yield of [(18)F]-L-FPTP was 21.1 ± 4.4% with a synthesis time of 60 min, the radiochemical purity was more than 99%. Biodistribution studies demonstrate high uptake of [(18)F]-L-FPTP in liver, kidney, pancreas, and blood at the early phase, and fast clearance in most tissues over the whole observed time. The uptake studies in Hepa1-6 cells suggest that [(18)F]-L-FPTP is transported by the amino acid transport system B(0,+), LAT2 and ASC. [(18)F]-L-FPTP displays good stability and is not incorporated into proteins in vitro. PET imaging shows that [(18)F]-L-FPTP can be a better potential PET tracer for differentiating tumor from inflammation than [(18)F]FDG and 5-(3-[(18)F]fluoroethyloxy)-L-tryptophan ([(18)F]-L-FEHTP), with high [(18)F]-L-FPTP uptake ratio (2.53) of tumor to inflammation at 60 min postinjection.
  
  
  CONCLUSIONS
  Using [(18)F]fluoropropyl derivatives as intermediates, the new tracer [(18)F]-L-FPTP was achieved with good yield and radiochemical purity, and the biological evaluation results of [(18)F]-L-FPTP showed that it was a hopeful tracer for PET tumor imaging.
authors.affiliation: PET-CT center, Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Shanzhen
authors.initials: S
authors.lastname: He
authors.forename: Ganghua
authors.initials: G
authors.lastname: Tang
authors.forename: Kongzhen
authors.initials: K
authors.lastname: Hu
authors.forename: Hongliang
authors.initials: H
authors.lastname: Wang
authors.forename: Shuxia
authors.initials: S
authors.lastname: Wang
authors.forename: Tingting
authors.initials: T
authors.lastname: Huang
authors.forename: Xiang
authors.initials: X
authors.lastname: Liang
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Tang
mesh_terms: D000818:Animals; D001692:Biological Transport; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D005260:Female; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: C586524:5-(3-fluoropropyloxy)tryptophan; D014364:Tryptophan
keywords: 5-(3-[(18)F]fluoropropyloxy)-L-tryptophan([(18)F]-L-FPTP); Biological evaluation; PET; Radiosynthesis