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

Journal of Nuclear Medicine

Matthias Bruehlmeier¹  Pius A. Schubiger¹  Ulrich Roelcke¹  Simon Mensah Ametamey¹ 

关键词: brain tumor;    hypoxia;    ¹⁸F-fluoromisonidazole;    PET;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown