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

IntroductionTrans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid (anti-[18F]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.MethodsKinetic assays for trans-1-amino-3-fluoro-[1-14C]cyclobutanecarboxylic acid ([14C]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 [14C]FACBC uptake using mammalian cell lines over-expressing system L amino acid transporter 1 or 2 (LAT1 or LAT2).ResultsASCT2 and SNAT2 transported [14C]FACBC with Michaelis–Menten kinetics Km values of 92.0 ± 32.3 μM and 222.0 ± 29.3 μM, respectively. LAT1 and LAT2 transported [14C]FACBC with Michaelis–Menten Km values of 230.4 ± 184.5 μM and 738.5 ± 87.6 μM, respectively.ConclusionsBoth 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-[18F]FACBC in cancer cells could be used for more effective prostate cancer imaging.