INTRODUCTION: Trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid (anti-[(18)F]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-(14)C]cyclobutanecarboxylic acid ([(14)C]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 [(14)C]FACBC uptake using mammalian cell lines over-expressing system L amino acid transporter 1 or 2 (LAT1 or LAT2). Results: ASCT2 and SNAT2 transported [14C]FACBC with Michaelis–Menten kinetics Km values of 96.7 ± 45.2 μM and 196.5 ± 19.7 μM, respectively. [correted]. LAT1 and LAT2 transported [(14)C]FACBC with Michaelis-Menten Km values of 230.4 ± 184.5 μM and 738.5 ± 87.6 μM, 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-[(18)F]FACBC in cancer cells could be used for more effective prostate cancer imaging.
INTRODUCTION:Trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid (anti-[(18)F]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-(14)C]cyclobutanecarboxylic acid ([(14)C]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 [(14)C]FACBC uptake using mammalian cell lines over-expressing system L amino acid transporter 1 or 2 (LAT1 or LAT2). Results:ASCT2 and SNAT2 transported [14C]FACBC with Michaelis–Menten kinetics Km values of 96.7 ± 45.2 μM and 196.5 ± 19.7 μM, respectively. [correted]. LAT1 and LAT2 transported [(14)C]FACBC with Michaelis-Menten Km values of 230.4 ± 184.5 μM and 738.5 ± 87.6 μM, 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-[(18)F]FACBC in cancer cells could be used for more effective prostate cancer imaging.
Authors: David M Schuster; Cristina Nanni; Stefano Fanti; Shuntaro Oka; Hiroyuki Okudaira; Yusuke Inoue; Jens Sörensen; Rikard Owenius; Peter Choyke; Baris Turkbey; Trond V Bogsrud; Tore Bach-Gansmo; Raghuveer K Halkar; Jonathon A Nye; Oluwaseun A Odewole; Bital Savir-Baruch; Mark M Goodman Journal: J Nucl Med Date: 2014-11-13 Impact factor: 10.057
Authors: F I Tade; W G Wiles; G Lu; B Bilir; O Akin-Akintayo; J S Lee; D Patil; W Yu; C Ormenisan Gherasim; B Fei; C S Moreno; A O Osunkoya; E J Teoh; S Oka; H Okudaira; M M Goodman; D M Schuster Journal: Amino Acids Date: 2018-06-15 Impact factor: 3.520