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Assessment of Hypoxia and Perfusion in Human Brain Tumors Using PET with ¹⁸F-Fluoromisonidazole and ¹⁵O-H₂O

¹ Paul Scherrer Institute, Center for Radiopharmaceutical Science, Villigen, Switzerland
² Department of Nuclear Medicine, Cantonal Hospital Aarau, Aarau, Switzerland
³ Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland

Hypoxia predicts poor treatment response of malignant tumors. We used PET with ¹⁸F-fluoromisonidazole (¹⁸F-FMISO) and ¹⁵O-H₂O to measure in vivo hypoxia and perfusion in patients with brain tumors. Methods: Eleven patients with various brain tumors were investigated. We performed dynamic ¹⁸F-FMISO PET, including arterial blood sampling and the determination of ¹⁸F-FMISO stability in plasma with high-performance liquid chromatography (HPLC). The ¹⁸F-FMISO kinetics in normal brain and tumor were assessed quantitatively using standard 2- and 3-compartment models. Tumor perfusion (¹⁵O-H₂O) was measured immediately before ¹⁸F-FMISO PET in 10 of the 11 patients. Results: PET images acquired 150–170 min after injection revealed increased ¹⁸F-FMISO tumor uptake in all glioblastomas. This increased uptake was reflected by ¹⁸F-FMISO distribution volumes >1, compared with ¹⁸F-FMISO distribution volumes <1 in normal brain. The ¹⁸F-FMISO uptake rate K₁ was also higher in all glioblastomas than in normal brain. In meningioma, which lacks the blood–brain barrier (BBB), a higher K₁ was observed than in glioblastoma, whereas the ¹⁸F-FMISO distribution volume in meningioma was <1. Pixel-by-pixel image analysis generally showed a positive correlation between ¹⁸F-FMISO tumor uptake at 0–5 min after injection and perfusion (¹⁵O-H₂O) with r values between 0.42 and 0.86, whereas late ¹⁸F-FMISO images (150–170 min after injection) were (with a single exception) independent of perfusion. Spatial comparison of ¹⁸F-FMISO with ¹⁵O-H₂O PET images in glioblastomas showed hypoxia both in hypo- and hyperperfused tumor areas. HPLC analysis showed that most of the ¹⁸F-FMISO in plasma was still intact 90 min after injection, accounting for 92%–96% of plasma radioactivity. Conclusion: Our data suggest that late ¹⁸F-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 ¹⁸F-FMISO uptake. The perfusion–hypoxia patterns described in glioblastoma suggest that hypoxia in these tumors may develop irrespective of the magnitude of perfusion.

Key Words: brain tumor • hypoxia • ¹⁸F-fluoromisonidazole • PET

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