UNLABELLED: Hypoxia predicts poor treatment response of malignant tumors. We used PET with (18)F-fluoromisonidazole ((18)F-FMISO) and (15)O-H(2)O to measure in vivo hypoxia and perfusion in patients with brain tumors. METHODS: Eleven patients with various brain tumors were investigated. We performed dynamic (18)F-FMISO PET, including arterial blood sampling and the determination of (18)F-FMISO stability in plasma with high-performance liquid chromatography (HPLC). The (18)F-FMISO kinetics in normal brain and tumor were assessed quantitatively using standard 2- and 3-compartment models. Tumor perfusion ((15)O-H(2)O) was measured immediately before (18)F-FMISO PET in 10 of the 11 patients. RESULTS: PET images acquired 150-170 min after injection revealed increased (18)F-FMISO tumor uptake in all glioblastomas. This increased uptake was reflected by (18)F-FMISO distribution volumes >1, compared with (18)F-FMISO distribution volumes <1 in normal brain. The (18)F-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 (18)F-FMISO distribution volume in meningioma was <1. Pixel-by-pixel image analysis generally showed a positive correlation between (18)F-FMISO tumor uptake at 0-5 min after injection and perfusion ((15)O-H(2)O) with r values between 0.42 and 0.86, whereas late (18)F-FMISO images (150-170 min after injection) were (with a single exception) independent of perfusion. Spatial comparison of (18)F-FMISO with (15)O-H(2)O PET images in glioblastomas showed hypoxia both in hypo- and hyperperfused tumor areas. HPLC analysis showed that most of the (18)F-FMISO in plasma was still intact 90 min after injection, accounting for 92%-96% of plasma radioactivity. CONCLUSION: Our data suggest that late (18)F-FMISO PET images provide a spatial description of hypoxia in brain tumors that is independent of BBB disruption and tumor perfusion. The distribution volume is an appropriate measure to quantify (18)F-FMISO uptake. The perfusion-hypoxia patterns described in glioblastoma suggest that hypoxia in these tumors may develop irrespective of the magnitude of perfusion.
UNLABELLED: Hypoxia predicts poor treatment response of malignant tumors. We used PET with (18)F-fluoromisonidazole ((18)F-FMISO) and (15)O-H(2)O to measure in vivo hypoxia and perfusion in patients with brain tumors. METHODS: Eleven patients with various brain tumors were investigated. We performed dynamic (18)F-FMISO PET, including arterial blood sampling and the determination of (18)F-FMISO stability in plasma with high-performance liquid chromatography (HPLC). The (18)F-FMISO kinetics in normal brain and tumor were assessed quantitatively using standard 2- and 3-compartment models. Tumor perfusion ((15)O-H(2)O) was measured immediately before (18)F-FMISO PET in 10 of the 11 patients. RESULTS: PET images acquired 150-170 min after injection revealed increased (18)F-FMISO tumor uptake in all glioblastomas. This increased uptake was reflected by (18)F-FMISO distribution volumes >1, compared with (18)F-FMISO distribution volumes <1 in normal brain. The (18)F-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 (18)F-FMISO distribution volume in meningioma was <1. Pixel-by-pixel image analysis generally showed a positive correlation between (18)F-FMISO tumor uptake at 0-5 min after injection and perfusion ((15)O-H(2)O) with r values between 0.42 and 0.86, whereas late (18)F-FMISO images (150-170 min after injection) were (with a single exception) independent of perfusion. Spatial comparison of (18)F-FMISO with (15)O-H(2)O PET images in glioblastomas showed hypoxia both in hypo- and hyperperfused tumor areas. HPLC analysis showed that most of the (18)F-FMISO in plasma was still intact 90 min after injection, accounting for 92%-96% of plasma radioactivity. CONCLUSION: Our data suggest that late (18)F-FMISO PET images provide a spatial description of hypoxia in brain tumors that is independent of BBB disruption and tumor perfusion. The distribution volume is an appropriate measure to quantify (18)F-FMISO uptake. The perfusion-hypoxia patterns described in glioblastoma suggest that hypoxia in these tumors may develop irrespective of the magnitude of perfusion.
Authors: Alexander M Spence; Mark Muzi; Kristin R Swanson; Finbarr O'Sullivan; Jason K Rockhill; Joseph G Rajendran; Tom C H Adamsen; Jeanne M Link; Paul E Swanson; Kevin J Yagle; Robert C Rostomily; Daniel L Silbergeld; Kenneth A Krohn Journal: Clin Cancer Res Date: 2008-05-01 Impact factor: 12.531