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

Mol Imaging Biol. 2014 Jun;16(3):322-9. doi: 10.1007/s11307-013-0693-0.


Purpose: 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).

Procedures: 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).

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Carboxylic Acids / pharmacokinetics*
  • Cell Line, Tumor
  • Cyclobutanes / pharmacokinetics*
  • Fluorine Radioisotopes / pharmacokinetics*
  • Fluorodeoxyglucose F18 / pharmacokinetics*
  • Humans
  • Hydrogen-Ion Concentration
  • Inflammation / metabolism*
  • Male
  • Methionine / analogs & derivatives*
  • Methionine / pharmacokinetics
  • Prostatic Neoplasms / metabolism*
  • Rats


  • Carboxylic Acids
  • Cyclobutanes
  • Fluorine Radioisotopes
  • Fluorodeoxyglucose F18
  • fluciclovine F-18
  • Methionine
  • methionine methyl ester