Uptake of [18F] EF5 as a Tracer for Hypoxic and Aggressive Phenotype in Experimental Head and Neck Squamous Cell Carcinoma1

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.