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

¹ Turku PET Centre, Turku, Finland
² Department of Oncology and Radiotherapy, University of Turku, Turku, Finland
³ Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
⁴ Turku PET Centre, Turku, FinlandDepartment of Oncology and Radiotherapy, University of Turku, Turku, Finland

^* To whom correspondence should be addressed. E-mail: gaber.komar{at}tyks.fi.

	Abstract

The aim of this study was to evaluate 2-(2-nitro-¹H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) labeled with ¹⁸F-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 ¹⁸F-EF5 PET/CT scan. On a separate day, ¹⁸F-FDG PET/CT was performed to determine the metabolically active tumor volume. In 6 patients, dynamic ¹⁸F-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. ¹⁸F-EF5 uptake in tumors was compared with that in neck muscle, and the ¹⁸F-EF5 findings were correlated with the ¹⁸F-FDG PET/CT studies. Results: A total of 13 primary tumors and 5 lymph node metastases were evaluated for their uptake of ¹⁸F-EF5. The median tumor-to-muscle ¹⁸F-EF5 uptake ratio (T/M) increased over time 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 ¹⁸F-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 ¹⁸F-EF5 to detect hypoxia in HNSCC is encouraging. Further development of ¹⁸F-EF5 for eventual targeting of antihypoxia therapies is warranted.

Key Words: head and neck cancer, hypoxia, ¹⁸F-EF5, squamous cell carcinoma

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