title: Synthesis and evaluation of 2-amino-5-(4-[(18)F]fluorophenyl)pent-4-ynoic acid ([(18)F]FPhPA): a novel (18)F-labeled amino acid for oncologic PET imaging.
abstract: BACKGROUND
  (18)F-labeled amino acids are important PET radiotracers for molecular imaging of cancer. This study describes synthesis and radiopharmacological evaluation of 2-amino-5-(4-[(18)F]fluorophenyl)pent-4-ynoic acid ([(18)F]FPhPA) as a novel amino acid radiotracer for oncologic imaging.
  
  
  METHODS
  (18)F]FPhPA was prepared using Pd-mediated Sonogashira cross-coupling reaction between 4-[(18)F]fluoroiodobenzene ([(18)F]FIB) and propargylglycine. The radiopharmacological profile of [(18)F]FPhPA was evaluated in comparison with O-(2-[(18)F]fluoroethyl)-L-tyrosine ([(18)F]FET) using the murine breast cancer cell line EMT6 involving cellular uptake studies, radiotracer uptake competitive inhibition experiments and small animal PET imaging.
  
  
  RESULTS
  (18)F]FPhPA was prepared in 42±10% decay-corrected radiochemical yield with high radiochemical purity >95% after semi-preparative HPLC purification. Cellular uptake of L-[(18)F]FPhPA reached a maximum of 58±14 % radioactivity/mg protein at 90 min. Lower uptake was observed for racemic and D-[(18)F]FPhPA. Radiotracer uptake inhibition studies by synthetic and naturally occurring amino acids suggested that Na(+)-dependent system ASC, especially ASCT2, and Na(+)-independent system L are important amino acid transporters for [(18)F]FPhPA uptake into EMT6 cells. Small animal PET studies demonstrated similar high tumor uptake of [(18)F]FPhPA in EMT6 tumor-bearing mice compared to [(18)F]FET reaching a maximum standardized uptake value (SUV) of 1.35 after 60 min p.i.. Muscle uptake of [(18)F]FPhPA was higher (SUV30min=0.65) compared to [(18)F]FET (SUV30min=0.40), whereas [(18)F]FPhPA showed a more rapid uptake and clearance from the brain compared to [(18)F]FET.
  
  
  CONCLUSIONS
  L-[(18)F]FPhPA is the first (18)F-labeled amino acid prepared through Pd-mediated cross-coupling reaction.
  
  
  CONCLUSIONS
  L-[(18)F]FPhPA displayed promising properties as a novel amino acid radiotracer for molecular imaging of system ASC and system L amino acid transporters in cancer.
authors.affiliation: Department of Oncology, University of Alberta, 11560 University Ave, Edmonton AB, T6G 1Z2, Canada.
authors.forename: Jenilee D
authors.initials: JD
authors.lastname: Way
authors.affiliation: Department of Oncology, University of Alberta, 11560 University Ave, Edmonton AB, T6G 1Z2, Canada.
authors.forename: Monica
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Oncology, University of Alberta, 11560 University Ave, Edmonton AB, T6G 1Z2, Canada.
authors.forename: Ingrit
authors.initials: I
authors.lastname: Hamann
authors.affiliation: Department of Oncology, University of Alberta, 11560 University Ave, Edmonton AB, T6G 1Z2, Canada.
authors.forename: Melinda
authors.initials: M
authors.lastname: Wuest
authors.affiliation: Department of Oncology, University of Alberta, 11560 University Ave, Edmonton AB, T6G 1Z2, Canada. Electronic address: wuest@ualberta.ca.
authors.forename: Frank
authors.initials: F
authors.lastname: Wuest
mesh_terms: D026962:Amino Acid Transport System ASC / Q000378:metabolism; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D024322:Amino Acids, Aromatic / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D015972:Gene Expression Regulation, Neoplastic; D007700:Kinetics; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D015778:Minor Histocompatibility Antigens; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D013696:Temperature
chemical_list: C000595849:2-amino-5-(4-fluorophenyl)pent-4-ynoic acid; D026962:Amino Acid Transport System ASC; D000596:Amino Acids; D024322:Amino Acids, Aromatic; D027283:Large Neutral Amino Acid-Transporter 1; D015778:Minor Histocompatibility Antigens; C498847:Slc1a4 protein, mouse; C498850:Slc1a5 protein, mouse
keywords: (18)F; Amino acid transporters; Amino acids; Positron emission tomography (PET); Sonogashira reaction; Tumor imaging