18F-HX4 hypoxia imaging with PET/CT in head and neck cancer: a comparison with 18F-FMISO

Objective Hypoxia is an important negative prognostic factor for radiation treatment of head and neck (H&N) cancer. The focus of this study was to evaluate the feasibility of F-18-HX4 (3-[F-18]fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3,-triazol-1-yl)-propan-1-ol) on hypoxia imaging compared with F-18-fluoromisonidazole (F-18-FMISO) mainly in human H&N cancer. Methods F-18-HX4 precursor, standards, and methods were provided by Siemens Molecular Imaging Inc. F-18-HX4 was prepared in an automated module. Twelve patients with H&N cancer were recruited into this study. Each patient underwent F-18-HX4 PET/CT imaging, followed by F-18-FMISO and F-18-fluorodeoxyglucose (F-18-FDG) PET/CT on separate days. F-18-HX4 and F-18-FMISO images of the H&N areas were acquired 1.5 and 2h after injection, respectively. Standard uptake values and tumor-to-muscle (T/M) ratios were calculated. Immunohistochemical analysis of the hypoxia-associated marker CA-IX was carried out to investigate the relationship with PET uptake. Results F-18-HX4 and F-18-FMISO in the patients gave similar hot spots well within the F-18-FDG uptake region. At 1.5h postinjection F-18-HX4 yielded a T/M similar to that of F-18-FMISO at 2h postinjection (1.94 +/- 1.03 vs. 1.85 +/- 1.01; P > 0.05). A total of 12 lesions were identified. Among them, eight lesions were positive and two lesions were negative on both F-18-HX4 and F-18-FM ISO images; one of the other two lesions was positive only on F-18-HX4, whereas the other one was positive only on F-18-FM ISO. The CA-IX expression result correlated with the hypoxia imaging but not with F-18-FDG imaging. Conclusion F-18-HX4 is a safe and feasible agent in hypoxia imaging of H&N cancer patients. We could assume that F-18-HX4 may have higher sensitivity and specificity, faster clearance, and shorter injection-acquisition time compared with traditional F-18-FMISO. Additional evaluations need to be carried out to validate the assumption. Further development of F-18-HX4 for eventual targeting of antihypoxia therapies is warranted. Nucl Med Commun 33:1096-1102 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.