18F-EF5: A New PET Tracer for Imaging Hypoxia in Head and Neck Cancer

The aim of this study was to evaluate 2-(2-nitro-H-1-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) labeled with F-18-fluorine to image hypoxia in patients with squamous cell carcinoma of the head and neck (HNSCC). Methods: Fifteen patients with HNSCC were studied. Measurement of tumor blood flow was followed by an F-18-EF5 PET/CT scan. On a separate day, F-18-FDG PET/CT was performed to determine the metabolically active tumor volume. In 6 patients, dynamic F-18-EF5 images of the head and neck area were acquired, followed by static images acquired at 1, 2, and 3 h after injection. In the remaining 9 patients, only static images were obtained. F-18-EF5 uptake in tumors was compared with that in neck muscle, and the F-18-EF5 findings were correlated with the F-18-FDG PET/CT studies. Results: A total of 13 primary tumors and 5 lymph node metastases were evaluated for their uptake of F-18-EF5. The median tumor-to-muscle F-18-EF5 uptake ratio (T/M) increased overtime and was 1.38 (range, 1.1-3.2) 3 h after tracer injection. The median blood flow in tumors was 36.7 mL/100 g/min (range, 23.3-78.6 mL/100 g/min). Voxel-by-voxel analysis of coregistered blood flow and F-18-EF5 images revealed a distinct pattern, resulting in a T/M of 1.5 at 3 h to be chosen as a cutoff for clinically significant hypoxia. Fourteen of 18 tumors (78%) had subvolumes within the metabolically active tumor volumes with T/M greater than or equal to 1.5. Conclusion: On the basis of these data, the potential of F-18-EF5 to detect hypoxia in HNSCC is encouraging. Further development of F-18-EFS for eventual targeting of antihypoxia therapies is warranted.