System A amino acid transport in cultured human tumor cells: implications for tumor imaging with PET.
The A system of amino acid transport is concentrative and thought to be a regulator of cell growth. The [11C]methyl alpha-aminoisobutyric acid (MeAIB) is prospectively an ideal tracer for transport measurements with PET, as it is not metabolized and concentrates in cells only via System A transport. We examined the factors governing [14C]MeAIB accumulation by cultured human erythroleukemic (K562) cells. Experiments were performed in growth medium and phosphate-buffered saline (PBS) +/- cycloheximide (an inhibitor of protein synthesis) on logarithmically growing cells, as well as cells that had reached a growth plateau. Both inward transport rate and net uptake of MeAIB were positively correlated with cell growth rate and showed a strong inverse relationship to amino acid supply. The observations are consistent with a body of evidence from animal tumor cells, and they suggest that the correlation between System A transport and tumor cell proliferation may be obscured in vivo by variations in amino acid supply. Thus, while [11C]MeAIB might be useful as a PET radiotracer of System A transport per se, this compound may be limited in its ability to provide measurements of tumor growth rate.
Bading
J R
JR
Department of Radiology, University of Southern California, Los Angeles 90033, USA.
Kan-Mitchell
J
J
Conti
P S
PS
D026905:Amino Acid Transport Systems; D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000000981:diagnostic imaging* / Q000378:metabolism*; D014055:Tomography, Emission-Computed; D014407:Tumor Cells, Cultured
D026905:Amino Acid Transport Systems; D000621:Aminoisobutyric Acids; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; C017911:2-(methylamino)isobutyric acid