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

J Nucl Med. 2004 Nov;45(11):1851-9.


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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Blood Flow Velocity
  • Brain / blood supply*
  • Brain / diagnostic imaging*
  • Brain Neoplasms / complications
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / physiopathology
  • Female
  • Humans
  • Hypoxia, Brain / diagnostic imaging*
  • Hypoxia, Brain / etiology
  • Hypoxia, Brain / physiopathology
  • Male
  • Middle Aged
  • Misonidazole / analogs & derivatives*
  • Oxygen Radioisotopes
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Subtraction Technique
  • Water*


  • Oxygen Radioisotopes
  • Radiopharmaceuticals
  • Water
  • fluoromisonidazole
  • Misonidazole