Investigation of transport mechanism and uptake kinetics of O-(2-[18F]fluoroethyl)-L-tyrosine in vitro and in vivo.
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 norbornane-carboxylic acid and a-(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 degrees 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 (t1/2 beta) 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.


CONCLUSIONS
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.
Heiss
P
P
Nuklearmedizinische Klinik and Poliklinik, Technische Universität München, Germany.
Mayer
S
S
Herz
M
M
Wester
H J
HJ
Schwaiger
M
M
Senekowitsch-Schmidtke
R
R
D000818:Animals; D001692:Biological Transport; D003287:Contrast Media / Q000493:pharmacokinetics*; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D006801:Humans; D007700:Kinetics; D051379:Mice; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D003287:Contrast Media; D005462:Fluorine Radioisotopes; C117289:O-(2-fluoroethyl)tyrosine; D014443:Tyrosine