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Imaging of Blood Flow and Hypoxia in Head and Neck Cancer: Initial Evaluation with [¹⁵O]H₂O and [¹⁸F]Fluoroerythronitroimidazole PET

Medicity Research Laboratory and Radiopharmaceutical Chemistry Laboratory, Turku PET Centre; Department of Oncology and Radiotherapy; and Department of Otorhinolaryngology and Head and Neck Surgery, Turku University Central Hospital, Turku, Finland

Hypoxia is a characteristic feature of malignant tumors that should be evaluated before the start of therapy. ¹⁸F-labeled fluoroerythronitroimidazole (FETNIM) is a possible candidate for imaging tumor hypoxia with PET. Quantitative analysis of [¹⁸F]FETNIM uptake in vivo is necessary before proceeding to assays predicting hypoxia. Methods: Eight patients with untreated head and neck squamous cell carcinoma were enrolled in the study. All patients underwent dynamic PET imaging with [¹⁸F]FETNIM, coupled with measurements of blood flow with [¹⁵O]H₂O and blood volume with [¹⁵O]CO. The metabolically active tumor volume was determined from [¹⁸F]FDG PET performed on a separate day. [¹⁸F]FETNIM uptake in the tumor was correlated with that in neck muscles and arterial plasma and compared with the findings of other PET studies. Results: Blood flow in tumor was 5- to 30-fold greater than in muscle, in contrast to blood volume, which did not significantly differ in the 2 tissues. With [¹⁸F]FETNIM PET, muscle activity remained invariably less than plasma activity, whereas activity in whole tumors was always greater than that in muscle. In 4 instances, the maximum tumor uptake of [¹⁸F]FETNIM was 1.2–2.0 times higher than plasma activity in the late dynamic phase. A kinetic model developed for calculation of distribution volume of reversibly trapping tracers was successfully applied in the [¹⁸F]FETNIM studies. Tumor distribution volume correlated strongly with the standardized uptake value of [¹⁸F]FETNIM between 60 and 120 min and with blood flow but not with the standardized uptake value of [¹⁸F]FDG. The relationship between [¹⁸F]FETNIM uptake and the blood flow of the tumor was less obvious on a pixel-by-pixel level. Conclusion: Uptake of [¹⁸F]FETNIM in head and neck cancer is highly variable and seems to be governed by blood flow at least in the early phase of tissue accumulation. Maximum tumor-to-muscle tracer uptake ratios > 180 min were in the range of 1–4, comparing favorably with those reported previously for [¹⁸F]fluoromisonidazole. Assessment of the distribution volume of [¹⁸F]FETNIM after the initial blood-flow phase is feasible for subsequent evaluation of hypoxia-specific retention.

Key Words: [¹⁸F]fluoroerythronitroimidazole • hypoxia • PET • head and neck cancer

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