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

• DOI: 10.1007/s11307-013-0693-0
• Publication Date: 2013-10-17T14:17:46Z
• Authors: Shuntaro Oka; Hiroyuki Okudaira; Masahiro Ono; David M. Schuster; Mark M. Goodman; Keiichi Kawai; Yoshifumi Shirakami
• Keywords: Inflammation; Male; Fluorine Radioisotopes; Carboxylic Acids; Prostatic Neoplasms; Hydrogen-Ion Concentration; Rats; 3. Good health; 03 medical and health sciences; Methionine; 0302 clinical medicine; Fluorodeoxyglucose F18; Cell Line, Tumor; Animals; Humans; Cyclobutanes

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).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.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).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).