title: Uptake of [18F]EF5 as a Tracer for Hypoxic and Aggressive Phenotype in Experimental Head and Neck Squamous Cell Carcinoma.
abstract: OBJECTIVE
  This study aims to investigate whether the uptake of 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide ([18F]EF5) and 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) is associated with a hypoxia-driven adverse phenotype in head and neck squamous cell carcinoma cell lines and tumor xenografts.
  
  
  METHODS
  Xenografts were imaged in vivo, and tumor sections were stained for hypoxia-inducible factor 1α (Hif-1α), carbonic anhydrase IX (CA IX), and glucose transporter 1 (Glut-1). Tracer uptakes and the expression of Hif-1α were determined in cell lines under 1% hypoxia.
  
  
  RESULTS
  High [18F]EF5 uptake was seen in xenografts expressing high levels of CA IX, Glut-1, and Hif-1α, whereas low [18F]EF5 uptake was detected in xenografts expressing low amounts of CA IX and Hif-1α. The uptake of [18F]EF5 between cell lines varied extensively under normoxic conditions. A clear correlation was found between the expression of Hif-1α and the uptake of [18F]FDG during hypoxia.
  
  
  CONCLUSIONS
  The UT-SCC cell lines studied differed with respect to their hypoxic phenotypes, and these variations were detectable with [18F]EF5. Acute hypoxia increases [18F]FDG uptake in vitro, whereas a high [18F]EF5 uptake reflects a more complex phenotype associated with hypoxia and an aggressive growth pattern.
authors.affiliation: MediCity Research Laboratory, Turku PET Centre, University of Turku, Turku, Finland; Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland.
authors.forename: Jonna
authors.initials: J
authors.lastname: Silén
authors.affiliation: Turku Centre of Biotechnology, University of Turku, Turku, Finland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Högel
authors.affiliation: Department of Pathology, University of Turku, Turku, Finland.
authors.forename: Katri
authors.initials: K
authors.lastname: Kivinen
authors.affiliation: MediCity Research Laboratory, Turku PET Centre, University of Turku, Turku, Finland; Department of Otorhinolaryngology, Turku University Hospital, Turku, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Silvoniemi
authors.affiliation: MediCity Research Laboratory, Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Sarita
authors.initials: S
authors.lastname: Forsback
authors.affiliation: Department of Biostatistics, University of Turku, Turku, Finland.
authors.forename: Eliisa
authors.initials: E
authors.lastname: Löyttyniemi
authors.affiliation: MediCity Research Laboratory, Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Olof
authors.initials: O
authors.lastname: Solin
authors.affiliation: Department of Otorhinolaryngology, Turku University Hospital, Turku, Finland.
authors.forename: Reidar
authors.initials: R
authors.lastname: Grénman
authors.affiliation: MediCity Research Laboratory, Turku PET Centre, University of Turku, Turku, Finland; Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Minn
authors.affiliation: Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland; Turku Centre of Biotechnology, University of Turku, Turku, Finland.
authors.forename: Panu M
authors.initials: PM
authors.lastname: Jaakkola
authors.affiliation: MediCity Research Laboratory, Turku PET Centre, University of Turku, Turku, Finland; Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland. Electronic address: tovgro@utu.fi.
authors.forename: Tove J
authors.initials: TJ
authors.lastname: Grönroos