Differentiation of tumour and inflammation: characterisation of [methyl-3H]methionine (MET) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) uptake in human tumour and inflammatory cells.
OBJECTIVE
Previous studies suggest that radiolabelled amino acids could be superior to FDG in differentiating tumour and inflammation. Therefore the aim of this study was to investigate the uptake of FET and MET in human tumour and inflammatory cells and to investigate their uptake kinetics.


METHODS
For uptake studies, cells were incubated with 370 kBq FET or 3.7 kBq MET for 15 min. Kinetic studies were performed at variable concentrations of FET and MET. Competitive inhibition studies were done with BCH, MeAIB and L: -serine.


RESULTS
All inflammatory cells incorporated more MET than the tumour cells. The uptake of FET, in contrast, was significantly lower in all inflammatory cells than in the tumour cells. In tumour cells the uptake of MET was about five times the uptake of FET. The competitive inhibitors reduced uptake of both tracers to 20-40% in tumour cells and to 70% in inflammatory cells. Kinetic studies showed that MET and FET transport was saturable in all cells except macrophages and followed a Michaelis-Menten kinetic. Highest capacity (V (max)) and affinity (K (m)) for the uptake of MET was observed in granulocytes. Capacity and affinity for FET uptake were highest in the DHL-4 cells.


CONCLUSIONS
In contrast to MET, FET accumulated to a significantly greater extent in tumour cells than in inflammatory cells. The marked differences between tumour and inflammatory cells concerning FET and MET uptake suggest that FET and MET are substrates of different subtypes of the L system.
Stöber
Barbara
B
Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675, Munich, Germany. senekowitsch@lrz.tu-muenchen.de
Tanase
Ursula
U
Herz
Michael
M
Seidl
Christof
C
Schwaiger
Markus
M
Senekowitsch-Schmidtke
Reingard
R
D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D003937:Diagnosis, Differential; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D008715:Methionine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D005462:Fluorine Radioisotopes; C117289:O-(2-fluoroethyl)tyrosine; D019275:Radiopharmaceuticals; D014443:Tyrosine; D008715:Methionine; C038344:methionine methyl ester