System A amino acid transport in cultured human tumor cells: implications for tumor imaging with PET

Nucl Med Biol. 1996 Aug;23(6):779-86. doi: 10.1016/0969-8051(96)00073-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems
  • Aminoisobutyric Acids* / pharmacokinetics
  • Carbon Radioisotopes
  • Carrier Proteins / metabolism*
  • Humans
  • Leukemia, Erythroblastic, Acute / diagnostic imaging*
  • Leukemia, Erythroblastic, Acute / metabolism*
  • Tomography, Emission-Computed
  • Tumor Cells, Cultured

Substances

  • Amino Acid Transport Systems
  • Aminoisobutyric Acids
  • Carbon Radioisotopes
  • Carrier Proteins
  • 2-(methylamino)isobutyric acid