Assessment of hypoxia and perfusion in human brain tumors using PET with F-18-fluoromisonidazole and O-15-H2O

Hypoxia predicts poor treatment response of malignant tumors. We used PET with F-18-fluoromisonidazole (F-18-FMISO) and (OH2O)-O-15 to measure in vivo hypoxia and perfusion in patients with brain tumors. Methods: Eleven patients with various brain tumors were investigated. We performed dynamic F-18-FMISO PET, including arterial blood sampling and the determination of F-18-FMISO stability in plasma with high-performance liquid chromatography (HPLC). The F-18-FMISO kinetics in normal brain and tumor were assessed quantitatively using standard 2-and 3-compartment models. Tumor per-fusion (O-15-H2O) was measured immediately before F-18-FMISO PET in 10 of the 11 patients. Results: PET images acquired 150-170 min after injection revealed increased F-18-FMISO tumor uptake in all glioblastomas. This increased uptake was reflected by F-18-FMISO distribution volumes >1, compared with F-18-FMISO distribution volumes <1 in normal brain. The F-18-FMISO uptake rate K-1 was also higher in all glioblastomas than in normal brain. In meningioma, which lacks the blood-brain barrier (BBB), a higher K-1 was observed than in glioblastoma, whereas the F-18-FMISO distribution volume in meningioma was <1. Pixel-by-pixel image analysis generally showed a positive correlation between F-18-FMISO tumor uptake at 0-5 min after injection and perfusion (O-15-H2O) with r values between 0.42 and 0.86, whereas late F-18-FMISO images (150-170 min after injection) were (with a single exception) independent of perfusion. Spatial comparison of F-18-FMISO with O-15-H2O PET images in glioblastomas showed hypoxia both in hypo- and hyperperfused tumor areas. HPLC analysis showed that most of the F-18-FMISO in plasma was still intact 90 min after injection, accounting for 92%-96% of plasma radioactivity. Conclusion: Our data suggest that late F-18-FMISO PET images provide a spatial description of hypoxia in brain tumors that is independent of BIBB disruption and tumor perfusion. The distribution volume is an appropriate measure to quantify F-18-FMISO uptake. The perfusion-hypoxia patterns described in glioblastoma suggest that hypoxia in these tumors may develop irrespective of the magnitude of perfusion.