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 18F-HX4 (3-[18F]fluoro-2-(4-((2-nitro-1Himidazol- 1-yl)methyl)-1H-1,2,3,-triazol-1-yl)-propan-1-ol) on hypoxia imaging compared with 18F-fluoromisonidazole (18F-FMISO) mainly in human H&N cancer.
Methods: 18F-HX4 precursor, standards, and methods were provided by Siemens Molecular Imaging Inc. 18F-HX4 was prepared in an automated module. Twelve patients with H&N cancer were recruited into this study. Each patient underwent 18F-HX4 PET/CT imaging, followed by 18F-FMISO and 18F-fluorodeoxyglucose (18F-FDG) PET/CT on separate days. 18F-HX4 and 18F-FMISO images of the H&N areas were acquired 1.5 and 2 h 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: 18F-HX4 and 18F-FMISO in the patients gave similar hot spots well within the 18F-FDG uptake region. At 1.5 h postinjection 18F-HX4 yielded a T/M similar to that of 18F-FMISO at 2 h 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 18F-HX4 and 18F-FMISO images; one of the other two lesions was positive only on 18F-HX4, whereas the other one was positive only on 18F-FMISO. The CA-IX expression result correlated with the hypoxia imaging but not with 18F-FDG imaging.
Conclusion: 18F-HX4 is a safe and feasible agent in hypoxia imaging of H&N cancer patients. We could assume that 18F-HX4 may have higher sensitivity and specificity, faster clearance, and shorter injection–acquisition time compared with traditional 18F-FMISO. Additional evaluations need to be carried out to validate the assumption. Further development of 18F-HX4 for eventual targeting of antihypoxia therapies is warranted.