Uptake of [18F]EF5 as a Tracer for Hypoxic and Aggressive Phenotype in Experimental Head and Neck Squamous Cell Carcinoma

Jonna Silén; Heidi Högel; Katri Kivinen; Antti Silvoniemi; Sarita Forsback; Eliisa Löyttyniemi; Olof Solin; Reidar Grénman; Heikki Minn; Panu M Jaakkola; Tove J Grönroos

doi:10.1016/j.tranon.2014.04.012

Uptake of [¹⁸F]EF5 as a Tracer for Hypoxic and Aggressive Phenotype in Experimental Head and Neck Squamous Cell Carcinoma

Transl Oncol. 2014 May 23;7(3):323-330. doi: 10.1016/j.tranon.2014.04.012. Online ahead of print.

Authors

Affiliations

¹ MediCity Research Laboratory, Turku PET Centre, University of Turku, Turku, Finland; Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland.
² Turku Centre of Biotechnology, University of Turku, Turku, Finland.
³ Department of Pathology, University of Turku, Turku, Finland.
⁴ MediCity Research Laboratory, Turku PET Centre, University of Turku, Turku, Finland; Department of Otorhinolaryngology, Turku University Hospital, Turku, Finland.
⁵ MediCity Research Laboratory, Turku PET Centre, University of Turku, Turku, Finland.
⁶ Department of Biostatistics, University of Turku, Turku, Finland.
⁷ Department of Otorhinolaryngology, Turku University Hospital, Turku, Finland.
⁸ Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland; Turku Centre of Biotechnology, University of Turku, Turku, Finland.
⁹ 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.

Abstract

Purpose: 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.