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.