18F-fluoromisonidazole dynamic positron emission tomography (dPET) is used to identify tumor hypoxia non-invasively. Its routine clinical implementation, however, has been hampered by the long acquisition times required. We investigated the feasibility of kinetic modeling using shortened acquisition times in 18F-fluoromisonidazole dPET, with the goal of expediting the clinical implementation of 18F-fluoromisonidazole dPET protocols. Methods: Six patients with squamous cell carcinoma of the head and neck and ten HT29 colorectal carcinoma-bearing nude rats were studied. In addition to an 18F-fluorodeoxyglucose PET scan, each patient underwent a 45-min 18F-fluoromisonidazole dPET scan, followed by 10 min acquisitions at 96±4 and 163±17 min post-injection. Ninety-minute 18F-fluoromisonidazole dPET acquisitions were performed in animals. Intra-tumor voxels were classified into 4 clusters based on their kinetic behavior using k-means clustering. Kinetic modeling was carried out using the foregoing full datasets (FD) and repeated for each of two shortened datasets corresponding to the first ~100 min (SD1; patients only) or the first 45 min (SD2) of dPET data. The kinetic rate constants (KRCs) as calculated with a 2-compartment model for both SD1 and SD2 were compared to those derived from FD by correlation (Pearson), regression (Passing-Bablok), deviation (Bland-Altman) and classification (area under receiver operating characteristic curve; AUC) analyses. Simulations were performed to assess uncertainties due to statistical noise. Results: Strong correlation (r≥0.75, p<0.001) existed between all KRCs deduced from both SD1 and SD2, and from FD. Significant differences between KRCs were only found for FD-SD2 correlations in patient studies. K1 and k3 were reproducible to within ~6% and ~30% (FD-SD1; patients) and ~4% and ~75% (FD-SD2; animals). AUC values for classification of patient clusters as hypoxic, using a tumor-to-blood ratio>1.2, were 0.91 (SD1) and 0.86 (SD2). The percentage standard deviation in estimating K1 and k3 from 45-min shortened datasets due to noise was <1% and between 2-12% respectively. Conclusion: Using single-session 45-min shortened 18F-fluoromisonidazole dynamic PET datasets appears to be adequate for the identification of intra-tumor regions of hypoxia. However, k3 was significantly overestimated in the clinical cohort. Further studies are necessary to evaluate the clinical significance of differences between the results as calculated from full and shortened datasets.
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