Preclinical Evaluation of 4-[ 18 F]Fluoroglutamine PET to Assess ASCT2 Expression in Lung Cancer

Purpose Alanine-serine-cysteine transporter 2 (ASCT2) expression has been demonstrated as a promising lung cancer biomarker. (2 S ,4 R )-4-[ 18 F]Fluoroglutamine (4-[ 18 F]fluoro-Gln) positron emission tomography (PET) was evaluated in preclinical models of non-small cell lung cancer as a quantitative, non-invasive measure of ASCT2 expression. Procedures In vivo microPET studies of 4-[ 18 F]fluoro-Gln uptake were undertaken in human cell line xenograft tumor-bearing mice of varying ASCT2 levels, followed by a genetically engineered mouse model of epidermal growth factor receptor (EGFR)-mutant lung cancer. The relationship between a tracer accumulation and ASCT2 levels in tumors was evaluated by IHC and immunoblotting. Result 4-[ 18 F]Fluoro-Gln uptake, but not 2-deoxy-2-[ 18 F]fluoro-D-glucose, correlated with relative ASCT2 levels in xenograft tumors. In genetically engineered mice, 4-[ 18 F]fluoro-Gln accumulation was significantly elevated in lung tumors, relative to normal lung and cardiac tissues. Conclusions 4-[ 18 F]Fluoro-Gln PET appears to provide a non-invasive measure of ASCT2 expression. Given the potential of ASCT2 as a lung cancer biomarker, this and other tracers reflecting ASCT2 levels could emerge as precision imaging diagnostics in this setting.