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-(1)H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) labeled with (18)F-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 (18)F-EF5 PET/CT scan. On a separate day, (18)F-FDG PET/CT was performed to determine the metabolically active tumor volume. In 6 patients, dynamic (18)F-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. (18)F-EF5 uptake in tumors was compared with that in neck muscle, and the (18)F-EF5 findings were correlated with the (18)F-FDG PET/CT studies.


RESULTS
A total of 13 primary tumors and 5 lymph node metastases were evaluated for their uptake of (18)F-EF5. The median tumor-to-muscle (18)F-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 (18)F-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.


CONCLUSIONS
On the basis of these data, the potential of (18)F-EF5 to detect hypoxia in HNSCC is encouraging. Further development of (18)F-EF5 for eventual targeting of antihypoxia therapies is warranted.
Komar
Gaber
G
Turku PET Centre, Turku, Finland. gaber.komar@tyks.fi
Seppänen
Marko
M
Eskola
Olli
O
Lindholm
Paula
P
Grönroos
Tove J
TJ
Forsback
Sarita
S
Sipilä
Hannu
H
Evans
Sydney M
SM
Solin
Olof
O
Minn
Heikki
H
D000328:Adult; D000368:Aged; D018288:Carcinoma, Small Cell / Q000000981:diagnostic imaging* / Q000378:metabolism*; D015687:Cell Hypoxia; D017341:Etanidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D055815:Young Adult; D005466:Fluorocarbons
D017341:Etanidazole; D005462:Fluorine Radioisotopes; D006845:Hydrocarbons, Fluorinated; D010100:Oxygen; D019275:Radiopharmaceuticals; C096011:2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide; D005466:Fluorocarbons