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

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.

• Authors: J R Bading, J Kan-Mitchell, P S Conti
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 23 Issue 6 Pg. 779-86 (Aug 1996) ISSN: 0969-8051 [Print] United States
• PMID: 8940721 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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