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

• Published in: Translational oncology Vol. 7; no. 3; pp. 323 - 330
• Main Authors: Silén, Jonna, Högel, Heidi, Kivinen, Katri, Silvoniemi, Antti, Forsback, Sarita, Löyttyniemi, Eliisa, Solin, Olof, Grénman, Reidar, Minn, Heikki, Jaakkola, Panu M, Grönroos, Tove J
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2014
• Subjects: Oncology
• ISSN: 1936-5233
• DOI: 10.1016/j.tranon.2014.04.012

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 ([18 F]EF5) and 2-deoxy-2-[18 F]fluoro- d -glucose ([18 F]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 i n 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 [18 F]EF5 uptake was seen in xenografts expressing high levels of CA IX, Glut-1, and Hif-1α, whereas low [18 F]EF5 uptake was detected in xenografts expressing low amounts of CA IX and Hif-1α. The uptake of [18 F]EF5 between cell lines varied extensively under normoxic conditions. A clear correlation was found between the expression of Hif-1α and the uptake of [18 F]FDG during hypoxia. CONCLUSIONS: The UT-SCC cell lines studied differed with respect to their hypoxic phenotypes, and these variations were detectable with [18 F]EF5. Acute hypoxia increases [18 F]FDG uptake in vitro , whereas a high [18 F]EF5 uptake reflects a more complex phenotype associated with hypoxia and an aggressive growth pattern.