Abstract
Purpose
Alanine-serine-cysteine transporter 2 (ASCT2) expression has been demonstrated as a promising lung cancer biomarker. (2S,4R)-4-[18F]Fluoroglutamine (4-[18F]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-[18F]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-[18F]Fluoro-Gln uptake, but not 2-deoxy-2-[18F]fluoro-D-glucose, correlated with relative ASCT2 levels in xenograft tumors. In genetically engineered mice, 4-[18F]fluoro-Gln accumulation was significantly elevated in lung tumors, relative to normal lung and cardiac tissues.
Conclusions
4-[18F]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.
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Acknowledgments
This work was supported by the Lung Cancer Research Foundation (LCRF), Vanderbilt Center for Molecular Probes (VCMP), NIH (ICMIC P50-CA128323, 2RO1CA102353, U01CA152662, P50-CA090949, P50-CA128323, P30-DK058404), and Kleberg Foundation.
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The authors declare that they have no conflict of interest.
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Mohamed Hassanein and Matthew R. Hight contributed equally to this work.
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Hassanein, M., Hight, M.R., Buck, J.R. et al. Preclinical Evaluation of 4-[18F]Fluoroglutamine PET to Assess ASCT2 Expression in Lung Cancer. Mol Imaging Biol 18, 18–23 (2016). https://doi.org/10.1007/s11307-015-0862-4
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DOI: https://doi.org/10.1007/s11307-015-0862-4