Kinetic analyses of trans-1-amino-3[18F]fluorocyclobutanecarboxylic acid transport in Xenopus laevis oocytes expressing human ASCT2 and SNAT2

Introduction: Trans-1-amino-3[F-18]fluorocyclobutanecarboxylic acid (anti-[F-18]FACBC) is a promising amino acid positron emission tomography (PET) radiotracer for visualizing prostate cancer. We previously showed that anti-FACBC is transported by amino acid transporters, especially by alanine-serine-cysteine transporter 2 (ASCT2), which is associated with tumor growth. We studied this affinity to assess the mechanism of anti-FACBC transport in prostate cancer cells. Methods: Kinetic assays for trans-1-amino-3-fluoro-[1-C-14]cyclobutanecarboxylic acid ([C-14]FACBC) were performed in Xenopus laevis oocytes over-expressing either ASCT2 or sodium-coupled neutral amino acid transporter 2 (SNAT2), both of which are highly expressed in prostate cancer cells. We also examined the kinetics of [C-14]FACBC uptake using mammalian cell lines over-expressing system L amino acid transporter 1 or 2 (LAT1 or LAT2). Results: ASCT2 and SNAT2 transported [C-14]FACBC with Michaelis-Menten kinetics K-m values of 92.0 +/- 32.3 mu M and 222.0 +/- 293 mu M, respectively. LAT1 and LAT2 transported [C-14]FACBC with Michaelis-Menten K-m values of 230.4 +/- 184.5 mu M and 738.5 +/- 87.6 mu M, respectively. Conclusions: Both ASCT2 and SNAT2 recognize anti-FACBC as a substrate. Anti-FACBC has higher affinity for ASCT2 than for SNAT2, LAT1, or LAT2. The ASCT2-preferential transport of anti-[F-18]FACBC in cancer cells could be used for more effective prostate cancer imaging. (C) 2013 Elsevier Inc. All rights reserved.