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).

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.

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.

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.