Mohamed Hassanein1,2, Matthew R Hight3,4, Jason R Buck3,4, Mohammed N Tantawy3,4, Michael L Nickels3,4, Megan D Hoeksema1, Bradford K Harris1, Kelli Boyd5, Pierre P Massion1,2,6, H Charles Manning7,8,9,10. 1. Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA. 2. Thoracic Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. 3. Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, Nashville, TN, 37232, USA. 4. Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. 5. Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. 6. Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. 7. Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu. 8. Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu. 9. Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu. 10. Program in Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu.
Abstract
PURPOSE: Alanine-serine-cysteine transporter 2 (ASCT2) expression has been demonstrated as a promising lung cancer biomarker. (2S,4R)-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.
PURPOSE:Alanine-serine-cysteine transporter 2 (ASCT2) expression has been demonstrated as a promising lung cancer biomarker. (2S,4R)-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.
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