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Purpose: 18F-fluoromisonidazole (18F-FMISO) is the most widely used positron emission tomography (PET) tracer for imaging tumor hypoxia. Previous reports suggested that the time from injection to the scan may affect the assessment of 18F-FMISO uptake. Herein, we directly compared the images at 2 h and 4 h after a single injection of 18F-FMISO. Methods: Twenty-three patients with or suspected of having a brain tumor were scanned twice at 2 and 4 h following an intravenous injection of 18F-FMISO. We estimated the mean standardized uptake value (SUV) of the gray matter and white matter and the gray-to-white matter ratio in the background brain tissue from the two scans. We also performed a semi-quantitative analysis using the SUVmax and maximum tumor-to-normal ratio (TNR) for the tumor. Results: At 2 h, the SUVmean of gray matter was significantly higher than that of white matter (median 1.23, interquartile range (IQR) 1.10–1.32 vs. 1.04, IQR 0.95–1.16, p < 0.0001), whereas at 4 h, it significantly decreased to approach that of the white matter (1.10, IQR 1.00–1.23 vs. 1.02, IQR 0.93–1.13, p = NS). The gray-to-white matter ratio thus significantly declined from 1.17 (IQR 1.14–1.19) to 1.09 (IQR 1.07–1.10) (p < 0.0001). All 7 patients with glioblastoma showed significant increases in the SUVmax (2.20, IQR 1.67–3.32 at 2 h vs. 2.65, IQR 1.74–4.41 at 4 h, p = 0.016) and the TNR (1.75, IQR 1.40–2.38 at 2 h vs. 2.34, IQR 1.67–3.60 at 4 h, p = 0.016). Conclusion: In the assessment of hypoxic tumors, 18F-FMISO PET for hypoxia imaging should be obtained at 4 h rather than 2 h after the injection. [ABSTRACT FROM AUTHOR]

Purpose: Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. Experimental Design: Glioblastoma patients ( n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV × FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. Results: All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS ( p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS ( p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV, patients' age, or Karnofsky performance scale (KPS) was significantly correlated with PSF or OS. The hMTV and hTLG were found to be independent factors affecting PFS and OS on multivariate analysis. Conclusions: We introduced hMTV and hTLG using FDG and FMISO PET to define metabolically active hypoxic volume. Univariate and multivariate analyses demonstrated that both hMTV and hTLG are significant predictors for PFS and OS in glioblastoma patients. [ABSTRACT FROM AUTHOR]