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 b e a regulator of cell growth. The [C-11]methyl alpha-aminoisobutyric a cid (MeAIB) is prospectively an ideal tracer for transport measurement s with PET, as it is not metabolized and concentrates in cells only vi a System A transport. We examined the factors governing [C-14]MeAIB ac cumulation by cultured human erythroleukemic (K562) cells. Experiments were performed in growth medium and phosphate-buffered saline (PBS) /- cycloheximide (an inhibitor of protein synthesis) on logarithmicall y growing cells, as well as cells that had reached a growth plateau. B oth inward transport rate and net uptake of MeAIB were positively corr elated with cell growth rate and showed a strong inverse relationship to amino acid supply. The observations are consistent with a body of e vidence from animal tumor cells, and they suggest that the correlation between System A transport and tumor cell proliferation may be obscur ed in vivo by variations in amino acid supply. Thus, while [C-11]MeAIB might be useful as a PET radiotracer of System A transport per se, th is compound may be limited in its ability to provide measurements of t umor growth rate.