3-fluoro-2-(4-((2-nitro-1h-imidazol-1-yl)methyl)-1h-1-2-3-triazol-1-yl)propan-1-ol and Head-and-Neck-Neoplasms

Hypoxia is an important factor influencing tumor progression and treatment efficacy. The aim of this study was to investigate the repeatability of hypoxia PET imaging with [(18)F]HX4 in patients with head and neck and lung cancer.. Nine patients with lung cancer and ten with head and neck cancer were included in the analysis (NCT01075399). Two sequential pretreatment [(18)F]HX4 PET/CT scans were acquired within 1 week. The maximal and mean standardized uptake values (SUVmax and SUVmean) were defined and the tumor-to-background ratios (TBR) were calculated. In addition, hypoxic volumes were determined as the volume of the tumor with a TBR >1.2 (HV1.2). Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated. To evaluate the spatial repeatability of the uptake, the PET/CT images were registered and a voxel-wise comparison of the uptake was performed, providing a correlation coefficient.. All parameters of [(18)F]HX4 uptake were significantly correlated between scans: SUVmax (r = 0.958, p < 0.001), SUVmean (r = 0.946, p < 0.001), TBRmax (r = 0.962, p < 0.001) and HV1.2 (r = 0.995, p < 0.001). The relative coefficients of repeatability were 15 % (SUVmean), 17 % (SUVmax) and 17 % (TBRmax). Voxel-wise analysis of the spatial uptake pattern within the tumors provided an average correlation of 0.65 ± 0.14.. Repeated hypoxia PET scans with [(18)F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [(18)F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments.

Topics: Aged; Biological Transport; Cell Hypoxia; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Male; Middle Aged; Nitroimidazoles; Positron-Emission Tomography; Prospective Studies; Reproducibility of Results; Triazoles

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.. 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.. 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.. 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.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Hypoxia; Feasibility Studies; Female; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Male; Middle Aged; Misonidazole; Multimodal Imaging; Nitroimidazoles; Positron-Emission Tomography; Tomography, X-Ray Computed; Triazoles