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L-Type Amino Acid Transporters LAT1 and LAT4 in Cancer: Uptake of 3-O-Methyl-6- ¹⁸F-Fluoro-L-Dopa in Human Adenocarcinoma and Squamous Cell Carcinoma In Vitro and In Vivo

¹ Department of Radiopharmaceutical Biology, Institute of Radiopharmacy, Research Center Dresden–Rossendorf, Dresden, Germany; and ² ABX Advanced Biochemical Compounds GmbH, Radeberg, Germany

Correspondence: For correspondence or reprints contact: Cathleen Haase, PhD, Department of Radiopharmaceutical Biology, Institute of Radiopharmacy, Research Center Dresden–Rossendorf, P.O. Box 51 01 19, 01314 Dresden, Germany. E-mail: c.haase{at}fzd.de

Expression of system L amino acid transporters (LAT) is strongly increased in many types of tumor cells. The purpose of this study was to demonstrate that ¹⁸F-labeled amino acids, for example, 3-O-methyl-6-¹⁸F-fluoro-L-dopa (¹⁸F-OMFD), that accumulate in tumors via LAT represent an important class of imaging agents for visualization of tumors in vivo by PET. Methods: ¹⁸F-OMFD uptake kinetics, transport inhibition, and system L messenger RNA expression were studied in vitro in human adenocarcinoma (HT-29), squamous cell carcinoma (FaDu), macrophages (THP-1), and primary aortic endothelial cells (HAEC) and in vivo in the corresponding mouse tumor xenograft models. Results: Uptake of ¹⁸F-OMFD in all cell lines tested was mediated mainly by the sodium-independent high-capacity LAT. We found higher uptake in FaDu cells (V_max, 10.6 ± 1.1 nmol/min x mg of cell protein) and in the corresponding FaDu tumor xenografts than in the other cells and corresponding xenograft models studied. Quantitative messenger RNA analysis revealed that tumor cells and xenografts have a higher expression of LAT1 than do HAEC and THP-1 macrophages. However, only in the FaDu tumor model did an increased ¹⁸F-OMFD uptake seem to be explained by increased LAT expression. Furthermore, we demonstrated a high expression of LAT4, a recently identified LAT. Conclusion: Our findings support the hypothesis that ¹⁸F-OMFD is a tracer for visualization of tumor cells. ¹⁸F-OMFD particularly seems to be a suitable tracer for diagnostic imaging of amino acid transport in poorly differentiated squamous cell head and neck carcinoma with increased LAT1 and LAT4 expression.

Key Words: L-type amino acid transporters • tumor cell lines • tumor xenograft models • monocyte/macrophage cell line • primary aortic endothelial cells

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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