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Investigation of Transport Mechanism and Uptake Kinetics of O-(2-[¹⁸F]Fluoroethyl)-L-Tyrosine In Vitro and In Vivo

Nuklearmedizinische Klinik and Poliklinik, Technische Universität München, Munich, Germany

Correspondence: For correspondence and reprints contact: Reingard Senekowitsch-Schmidtke, MD, PhD, Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, Ismaningerstr. 22, D-81675 Munich, Germany.

ABSTRACT

The aim of the study was to investigate the transport mechanism and uptake kinetics of the new ¹⁸F-labeled amino acid O-(2-[¹⁸F]fluoroethyl)-L-tyrosine (L-[¹⁸F]FET) and D-[¹⁸F]FET in human SW 707 colon carcinoma cells and the in vivo biodistribution of this tracer in SW 707 tumor-bearing mice. Methods: SW 707 cells were incubated with L- and D-[¹⁸F]FET under physiologic amino acid concentrations with and without the competitive transport inhibitors 2-amino-2 norbomane-carboxylic acid and -(methylamino)isobutyric acid plus serine. For the investigation of the transport capacity, unlabeled L-FET was added to the samples. In addition, xenotransplanted mice were injected intravenously with L-[¹⁸F]FET; killed 10, 30, 60 and 120 min after injection; and the radioactivity concentration in different organs was measured in a gamma counter. Results: The in vitro kinetic experiments showed a fast initial uptake of L-[¹⁸F]FET into the cells up to 6 min, followed by a nearly constant tracer concentration. The accumulation factor, calculated as the ratio between intracellular and extracellular tracer concentration, ranged from 3.0 to 5.0. In comparison, D-[¹⁸F]FET did not accumulate in the cells. Washing the cells in medium at 37°C, after a 30-min incubation with L-[F-¹⁸]FET, led to a rapid decrease of radioactivity, which demonstrates the bidirectional transport. In addition, experiments with increasing concentrations of unlabeled L-FET indicated a linear correlation between L-FET uptake rate and the extracellular concentration. Results of transport inhibition experiments with the specific competitive inhibitors demonstrated that the uptake of L-FET into SW 707 cells was caused mainly (>80%) by the transport system L. In the in vivo studies, the half-life (t_{1/2 ß}) of L-[¹⁸F]FET in the plasma was determined to be 94 min and the uptake into the brain increased to 120 min with a brain-to-blood ratio of 0.86. The xenotransplanted tumor showed higher uptake of L-[¹⁸F]FET (>6 %ID/g) at 30 and 60 min than all other organs, except the pancreas. The tumor-to-blood ratio reached about 2 between 30 and 120 min. Conclusion: L-[¹⁸F]FET, which is transported by the specific amino acid transport system L, seems to be a potential amino acid tracer for tumor imaging and therapy monitoring with PET.

Key Words: PET • amino acids • O-(2-[¹⁸F]fluoroethyl)tyrosine • tumor imaging

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