title: Preclinical Evaluation of 4-[18F]Fluoroglutamine PET to Assess ASCT2 Expression in Lung Cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.|Thoracic Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hassanein
authors.affiliation: Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, Nashville, TN, 37232, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hight
authors.affiliation: Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, Nashville, TN, 37232, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Buck
authors.affiliation: Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, Nashville, TN, 37232, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
authors.forename: Mohammed N
authors.initials: MN
authors.lastname: Tantawy
authors.affiliation: Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, Nashville, TN, 37232, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nickels
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
authors.forename: Megan D
authors.initials: MD
authors.lastname: Hoeksema
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
authors.forename: Bradford K
authors.initials: BK
authors.lastname: Harris
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
authors.forename: Kelli
authors.initials: K
authors.lastname: Boyd
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.|Thoracic Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.|Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
authors.forename: Pierre P
authors.initials: PP
authors.lastname: Massion
authors.affiliation: Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu.|Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu.|Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu.|Program in Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu.
authors.forename: H Charles
authors.initials: HC
authors.lastname: Manning
mesh_terms: D026962:Amino Acid Transport System ASC / Q000378:metabolism*; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005973:Glutamine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D008819:Mice, Nude; D015778:Minor Histocompatibility Antigens; D009154:Mutation / Q000235:genetics; D049268:Positron-Emission Tomography / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: C569565:4-fluoroglutamine; D026962:Amino Acid Transport System ASC; D015778:Minor Histocompatibility Antigens; C420506:SLC1A5 protein, human; D005973:Glutamine; D066246:ErbB Receptors
keywords: ASCT2; Cancer; Glutamine; Lung; NSCLC; PET; SCC; SLC1A5; Transporter