title: Differences in transport mechanisms of trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid in inflammation, prostate cancer, and glioma cells: comparison with L-[methyl-11C]methionine and 2-deoxy-2-[18F]fluoro-D-glucose.
abstract: OBJECTIVE
  We aimed to elucidate trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid (anti-[(18)F]FACBC) uptake mechanisms in inflammatory and tumor cells, in comparison with those of L-[methyl-(11)C]methionine ([(11)C]Met) and 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG).
  
  
  METHODS
  Using carbon-14-labeled tracers, in vitro time-course, pH dependence, and competitive inhibition uptake experiments were performed in rat inflammatory (T cells, B cells, granulocytes, macrophages), prostate cancer (MLLB2), and glioma (C6) cells.
  
  
  RESULTS
  Anti-[(14)C]FACBC uptake ratios of T/B cells to tumor cells were comparable, while those of granulocytes/macrophages to tumor cells were lower than those for [(14)C]FDG. Over half of anti-[(14)C]FACBC uptake by T/B and tumor cells was mediated by Na(+)-dependent amino acid transporters (system ASC), whereas most [(14)C]Met transport in all cells was mediated by Na(+)-independent carriers (system L).
  
  
  CONCLUSIONS
  The low anti-[(18)F]FACBC accumulation in granulocytes/macrophages may be advantageous in discriminating inflamed regions from tumors. The significant anti-[(18)F]FACBC uptake in T/B cells may cause false-positives in some cancer patients who undergo FACBC-positron emission tomography (PET).
authors.affiliation: Research Center, Nihon Medi-Physics Co., Ltd, Chiba, Japan, shuntaro_oka@nmp.co.jp.
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Oka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okudaira
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.forename: David M
authors.initials: DM
authors.lastname: Schuster
authors.forename: Mark M
authors.initials: MM
authors.lastname: Goodman
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kawai
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Shirakami
mesh_terms: D000818:Animals; D002264:Carboxylic Acids / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D003503:Cyclobutanes / Q000493:pharmacokinetics*; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011471:Prostatic Neoplasms / Q000378:metabolism*; D051381:Rats
chemical_list: D002264:Carboxylic Acids; D003503:Cyclobutanes; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; C117460:fluciclovine F-18; D008715:Methionine; C038344:methionine methyl ester