title: ¹⁸F-HX4 hypoxia imaging with PET/CT in head and neck cancer: a comparison with ¹⁸F-FMISO.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: PET Center, Huashan Hospital, Fudan University, Shanghai, China.
authors: Limin
authors: L
authors: Chen
authors: Zhengwei
authors: Z
authors: Zhang
authors: Hartmuth C
authors: HC
authors: Kolb
authors: Joseph C
authors: JC
authors: Walsh
authors: James
authors: J
authors: Zhang
authors: Yihui
authors: Y
authors: Guan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015687:Cell Hypoxia; D005240:Feasibility Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives*; D064847:Multimodal Imaging / Q000379:methods*; D009593:Nitroimidazoles; D049268:Positron-Emission Tomography; D014057:Tomography, X-Ray Computed; D014230:Triazoles
chemical_list: C553729:3-fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)propan-1-ol; D014408:Biomarkers, Tumor; D009593:Nitroimidazoles; D014230:Triazoles; C031843:fluoromisonidazole; D008920:Misonidazole