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

Purpose

We aimed to elucidate trans-1-amino-3-¹⁸F]fluorocyclobutanecarboxylic acid (anti-¹⁸F]FACBC) uptake mechanisms in inflammatory and tumor cells, in comparison with those of l-methyl-¹¹C]methionine (¹¹C]Met) and 2-deoxy-2-¹⁸F]fluoro-d-glucose (¹⁸F]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-¹⁴C]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 ¹⁴C]FDG. Over half of anti-¹⁴C]FACBC uptake by T/B and tumor cells was mediated by Na⁺-dependent amino acid transporters (system ASC), whereas most ¹⁴C]Met transport in all cells was mediated by Na⁺-independent carriers (system L).

Conclusions

The low anti-¹⁸F]FACBC accumulation in granulocytes/macrophages may be advantageous in discriminating inflamed regions from tumors. The significant anti-¹⁸F]FACBC uptake in T/B cells may cause false-positives in some cancer patients who undergo FACBC-positron emission tomography (PET).