[18F]Fluoroazomycinarabinofuranoside (18FAZA) and [18F]Fluoromisonidazole (18FMISO): a comparative study of their selective uptake in hypoxic cells and PET imaging in experimental rat tumors

The present study compares the uptake of [18F]Fluoroazomycinarabinofuranoside (18FAZA), a recently developed hypoxia tracer for PET imaging of tissue hypoxia, with an established tracer [18F]Fluoromisonidazole (18FMISO) both in vitro, using Walker 256 rat carcinosarcoma cells, and in vivo in experimental rat tumors eleven to twelve days after tumor cell implantation. In vitro studies indicated that hypoxia-selective uptake of both 18FAZA and 18FMISO in tumor cells, 20 and 100 minutes post-incubation was of the same magnitude (20 min: 1.24 ± 0.4% (18FAZA); 1.19 ± 0.7% (18FMISO); 100 min: 3.6 ± 1.6% (18FAZA); 3.3 ± 1.7% (18FMISO)). PET imaging reflected a similar radiotracer distribution in rat tumors for 18FAZA and 18FMISO one h after radiotracer injection. The concentration of 18FAZA in the tumors as measured by PET, however, was lower in comparison to 18FMISO (SUVFAZA 0.61 ± 0.2 vs. SUVFMISO = 0.92 ± 0.3, p < 0.05) although the tumor to muscle ratios for 18FAZA and 18FMISO did not differ in the PET images that were obtained after one h (SUVFAZA = 2.5 ± 0.5 vs. SUVFMISO = 2.9 ± 0.7). A comparison of PET data three h post-injection (SUVFAZA = 3.0 ± 0.5 vs. SUVFMISO = 4.6 ± 1.8, p < 0.05) demonstrated a lower 18FAZA uptake that indicates a lower sensitivity of 18FAZA in comparison to 18FMISO in detecting hypoxic regions at a longer time in this animal model. However, these data also show a faster elimination of 18FAZA from blood, viscera and muscle tissue, via the renal system. This advantage of a faster reduction of unspecific binding, in light of similar or marginally lower tumor uptake, warrants further investigation of 18FAZA as a marker of regional hypoxia in tumors