Influence of the scan time point when assessing hypoxia in 18F-fluoromisonidazole PET: 2 vs. 4 h

  • Kentaro Kobayashi
  • Osamu Manabe
  • Kenji HirataEmail author
  • Shigeru Yamaguchi
  • Hiroyuki Kobayashi
  • Shunsuke Terasaka
  • Takuya Toyonaga
  • Sho Furuya
  • Keiichi Magota
  • Yuji Kuge
  • Kohsuke Kudo
  • Tohru Shiga
  • Nagara Tamaki
Original Article
Part of the following topical collections:
  1. Oncology – Brain



18F-fluoromisonidazole (18F-FMISO) is the most widely used positron emission tomography (PET) tracer for imaging tumor hypoxia. Previous reports suggested that the time from injection to the scan may affect the assessment of 18F-FMISO uptake. Herein, we directly compared the images at 2 h and 4 h after a single injection of 18F-FMISO.


Twenty-three patients with or suspected of having a brain tumor were scanned twice at 2 and 4 h following an intravenous injection of 18F-FMISO. We estimated the mean standardized uptake value (SUV) of the gray matter and white matter and the gray-to-white matter ratio in the background brain tissue from the two scans. We also performed a semi-quantitative analysis using the SUVmax and maximum tumor-to-normal ratio (TNR) for the tumor.


At 2 h, the SUVmean of gray matter was significantly higher than that of white matter (median 1.23, interquartile range (IQR) 1.10–1.32 vs. 1.04, IQR 0.95–1.16, p < 0.0001), whereas at 4 h, it significantly decreased to approach that of the white matter (1.10, IQR 1.00–1.23 vs. 1.02, IQR 0.93–1.13, p = NS). The gray-to-white matter ratio thus significantly declined from 1.17 (IQR 1.14–1.19) to 1.09 (IQR 1.07–1.10) (p < 0.0001). All 7 patients with glioblastoma showed significant increases in the SUVmax (2.20, IQR 1.67–3.32 at 2 h vs. 2.65, IQR 1.74–4.41 at 4 h, p = 0.016) and the TNR (1.75, IQR 1.40–2.38 at 2 h vs. 2.34, IQR 1.67–3.60 at 4 h, p = 0.016).


In the assessment of hypoxic tumors, 18F-FMISO PET for hypoxia imaging should be obtained at 4 h rather than 2 h after the injection.


Fluoromisonidazole Positron emission tomography Glioblastoma Hypoxia Scan timing This article is part of the Topical Collection on Oncology – Brain 



We thank the staff members of the Department of Nuclear Medicine, the Central Institute of Isotope Science, the Department of Cancer Pathology, Hokkaido University, and the Department of Radiology, Hokkaido University Hospital, for their support of this work.

Funding information

This research was supported in part by a Grant-in-Aid for General Scientific Research from the Japan Society for the Promotion of Science (Ko.Ke., 19K17127).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. A portion of our results were presented at the SNMMI 2018 Conference (J Nucl Med May 1, 2015, vol. 56 no. supplement 3373).

Informed consent

The requirement for written informed consent was waived due to the retrospective nature of this study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Kentaro Kobayashi
    • 1
  • Osamu Manabe
    • 1
  • Kenji Hirata
    • 1
    Email author
  • Shigeru Yamaguchi
    • 2
  • Hiroyuki Kobayashi
    • 3
  • Shunsuke Terasaka
    • 3
  • Takuya Toyonaga
    • 4
  • Sho Furuya
    • 1
  • Keiichi Magota
    • 5
  • Yuji Kuge
    • 6
  • Kohsuke Kudo
    • 7
    • 8
  • Tohru Shiga
    • 1
  • Nagara Tamaki
    • 9
  1. 1.Department of Diagnostic and Interventional RadiologyHokkaido University HospitalSapporoJapan
  2. 2.Department of NeurosurgeryHokkaido University Graduate School of MedicineSapporoJapan
  3. 3.Kashiwaba Neurosurgery HospitalSapporoJapan
  4. 4.Department of Radiology and Biomedical ImagingYale University School of MedicineNew HavenUSA
  5. 5.Division of Medical Imaging and TechnologyHokkaido University HospitalSapporoJapan
  6. 6.Central Institute of Isotope ScienceHokkaido UniversitySapporoJapan
  7. 7.Department of Diagnostic ImagingHokkaido University Graduate School of MedicineSapporoJapan
  8. 8.Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and EducationHokkaido UniversitySapporoJapan
  9. 9.Department of RadiologyKyoto Prefectural UniversityKyotoJapan

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