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

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).

• Authors: Shuntaro Oka, Hiroyuki Okudaira, Masahiro Ono, David M Schuster, Mark M Goodman, Keiichi Kawai, Yoshifumi Shirakami
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 16 Issue 3 Pg. 322-9 (Jun 2014) ISSN: 1860-2002 [Electronic] United States
• PMID: 24136390 (Publication Type: Comparative Study, Journal Article)

Chemical References

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

Topics

• 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, pharmacokinetics)
• Prostatic Neoplasms (metabolism)
• Rats