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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; and ³ Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

View larger version (9K): [in this window] [in a new window]   FIGURE 1.  Time course for scanning protocol of combined 15O-H2O and 18F-EF5 study. CTAC = computer-assisted tomography for attenuation correction.

View larger version (31K): [in this window] [in a new window]   FIGURE 2.  (A) Combined blood flow and early and late (3 h from injection) 18F-EF5 images in patient 1, who presented with right T4N0 base-of-tongue HNSCC. Note similarity of blood flow and early 18F-EF5 images (2 min from injection), showing doughnutlike appearance of tracer uptake in tumor. By contrast, 18F-EF5 image obtained 3 h after injection shows uptake in central, less perfused area. (B) Time–activity curves from same tumor as in A, demonstrating differential uptake kinetics of 18F-EF5 of peripheral (nonhypoxic) and central (hypoxic) parts of tumor. In well-perfused area, initial uptake of 18F-EF5 is higher than that in more hypoxic area; after first 15 min, reverse is true. With exception of first 90-s image, uptake in dorsal neck muscle and arterial blood remain lower than that in both tumor parts throughout 3-h acquisition time.

View larger version (10K): [in this window] [in a new window]   FIGURE 3.  Maximum and mean 18F-EF5 T/M ratios over all static emission image acquisition time points. (A) Mean T/M ratios increase from 1 through 3 h after injection. (B) Higher maximum T/M ratio and lower mean T/M ratio at 4 h after injection, when compared with 3 h after injection, could be explained by increasing image noise (and decreasing overall image quality).

View larger version (44K): [in this window] [in a new window]   FIGURE 4.  Examples of both PET and CT images for all 3 tracers for 3 patients. 18F-EF5 images are made at 3 h after injection. Arrows indicate primary tumors, and arrowheads indicate metastatic lesions.

View larger version (23K): [in this window] [in a new window]   FIGURE 5.  Relationship between uptake of 18F-EF5 at 3 h expressed as T/M and blood flow on voxel-by-voxel basis in all 18 primary and metastatic tumors. y-Axis indicates threshold value of 1.5, tentatively representing PHA. x-Axis indicates perfusion value of 30 mL/100 g/min, which represents border between poorly and well-perfused areas. Resulting are areas of high perfusion with good oxygenation (trend A), low perfusion with low oxygenation (trend B), and intermediate perfusion (trend C).

View larger version (6K): [in this window] [in a new window]   FIGURE 6.  Comparison of percentages of tumor subvolumes representing PHA using 3 different T/M 18F-EF5 uptake threshold values. MATV is determined from 18F-FDG study performed on separate day.