PURPOSE:Hypoxia is associated with aggressive tumour behaviour and can influence response to systemic therapy and radiotherapy. The prevalence of hypoxia in metastatic colorectal cancer is poorly understood, and the relationship of hypoxia to patient outcomes has not been clearly established. The aims of the study were to evaluate hypoxia in metastatic colorectal cancer with [18F]Fluoromisonidazole ([18F]FMISO PET) and correlate these findings with glycolytic metabolism ([18F]FDG PET) and angiogenic blood biomarkers and patient outcomes. METHODS:Patients with metastatic colorectal cancer received routine staging investigations and both [18F] FMISO PET and [18F] FDG PET scans. Correlative blood specimens were also obtained at the time of the [18F] FMISO PET scan. Patient follow-up was performed to establish progression-free survival. RESULTS:A total of 40 patients were recruited into the trial. [18F]FMISO and [18F]FDG PET scans showed a significant correlation of SUVmax (p = 0.003). A significant correlation of progression-free survival and [18F] FMISO TNR (p = 0.02) and overall survival with [18F]FMISO TNR (p = 0.003) and [18F]FDG TGV (p = 0.02) was observed. Serum levels of osteopontin, but not VEGF, correlated with [18F] FMISO and [18F]FDG PET scan parameters. CONCLUSION:[18F]FMISO PET uptake in metastatic colorectal cancer significantly correlates with glycolytic metabolism and is predictive of progression-free and overall survival. These findings have implications for the assessment and treatment of metastatic colorectal cancer patients with novel therapies which affect tumour angiogenesis and hypoxia.