3-O-methyl-6-18F-fluoro-L-dopa, a new tumor imaging agent: investigation of transport mechanism in vitro.
(18)F-Labeled amino acids represent a promising class of imaging agents in tumors, particularly brain tumors. However, the determination of their potential to image peripheral tumors, possibly depending on individual transport characteristics, still remains an area of investigation. The present study investigated the transport mechanism for 3-O-methyl-6-(18)F-fluoro-L-dopa (OMFD), a novel (18)F-labeled phenylalanine derivative, into tumor cells.


METHODS
OMFD has routinely and reliably been prepared for clinical use in 20%-25% radiochemical yield (decay corrected, related to (18)F-F(2)) using 6-(18)F-fluoro-L-3,4-dihydroxyphenylalanine preparation devices with minor modifications. In vitro uptake assays with HT-29 (human colon adenocarcinoma) cells, FaDu (squamous cell carcinoma) cells, and RBE4 (immortalized rat brain endothelial) cells were performed with OMFD under physiologic amino acid concentrations without and with the competitive transport inhibitors 2-aminobicyclo-[2,2,1]-heptane-2-carboxylic acid and alpha-(methylamino)isobutyric acid plus serine and without or with Na(+).


RESULTS
Transport inhibition experiments using specific competitive inhibitors demonstrated that uptake of OMFD in all cell lines tested was mediated mainly by the sodium-independent high-capacity amino acid transport systems. The highest OMFD uptake was in FaDu cells.


CONCLUSIONS
OMFD seems to be a promising PET tracer for imaging of amino acid transport in tumors.
Bergmann
Ralf
R
Institut fuer Bioanorganische und Radiopharmazeutische Chemie, PET Zentrum Rossendorf, Forschungszentrum Rossendorf, Dresden, Germany. r.bergmann@fz-rossendorf.de
Pietzsch
Jens
J
Fuechtner
Frank
F
Pawelke
Beate
B
Beuthien-Baumann
Bettina
B
Johannsen
Bernd
B
Kotzerke
Joerg
J
D000596:Amino Acids / Q000378:metabolism*; D000598:Amino Acids, Cyclic / Q000494:pharmacology; D000621:Aminoisobutyric Acids / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D051381:Rats; D012694:Serine / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D000621:Aminoisobutyric Acids; D005462:Fluorine Radioisotopes; C055151:3-O-methyl-6-fluoro-dopa; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; C017911:2-(methylamino)isobutyric acid; D012694:Serine; D004295:Dihydroxyphenylalanine; D012964:Sodium