Direct comparison of 2‑amino[3‑11C]isobutyric acid and 2‑amino[11C]methyl‑isobutyric acid uptake in eight lung cancer xenograft models

The non‑natural amino acid positron emission tomography tracers, 2‑amino[3‑11C]isobutyric acid ([3‑11C]AIB) and 2‑amino[11C]methyl‑isobutyric acid ([11C]MeAIB), are metabolically stable in vivo and accumulate in tumors. [3‑11C]AIB is transported into cells mainly via the amino acid transport system A and partially via systems L and ASC, whereas [11C]MeAIB is transported into cells specifically via system A. How transport via the different systems affects the tumor uptake of these tracers, however, is unclear. In the present study, the tumor uptake of the two tracers was directly compared in eight lung cancer models (A549, H82, H441, H460, H1299, H1650, PC14, and SY), and the correlation of tumor uptake with several factors (amino acid transporter expression, contribution of amino acid transport systems to AIB uptake and tumor proliferation indices) was analyzed. Biodistribution analyses revealed that the tumor uptake of [3‑11C]AIB (4.9 to 19.2% injected dose per gram [ID/g]) was higher than that of [11C]MeAIB (3.1 to 15.9% ID/g) in all eight tumors, with a statistically significant difference in three tumors (P0.01 in H441 and H460 tumors, P0.05 in H82 tumors). A significant correlation was observed between the tumor uptake of the two tracers (r=0.95, P0.01). The mRNA expression levels of the amino acid transporters of system A (SLC38A1 and SLC38A2), system L (SLC7A5) and system ASC (SLC1A5) were higher in all eight tumors than in the normal lung, with widely varying expression patterns. Although the contributions of the amino acid transport systems, Ki‑67 indices and tumor doubling times greatly differed among the eight models, these factors did not correlate with the tumor uptake of either tracer. The higher tumor uptake of [3‑11C]AIB and the correlation of tumor uptake between [3‑11C]AIB and [11C]MeAIB warrant further investigation in clinical studies in order to clarify the role of [3‑11C]AIB PET in oncology imaging.