18F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors

  • Takuya Toyonaga
  • Kenji Hirata
  • Shigeru YamaguchiEmail author
  • Kanako C. Hatanaka
  • Sayaka Yuzawa
  • Osamu Manabe
  • Kentaro Kobayashi
  • Shiro Watanabe
  • Tohru Shiga
  • Shunsuke Terasaka
  • Hiroyuki Kobayashi
  • Yuji Kuge
  • Nagara Tamaki
Original Article



Tumor necrosis is one of the indicators of tumor aggressiveness. 18F-fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoral necrosis can be detected by FMISO PET in brain tumors regardless of their histopathology. We applied FMISO PET to various types of brain tumors before tumor resection and evaluated the correlation between histopathological necrosis and FMISO uptake.


This study included 59 brain tumor patients who underwent FMISO PET/computed tomography before any treatments. According to the pathological diagnosis, the brain tumors were divided into three groups: astrocytomas (group 1), neuroepithelial tumors except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumor was evaluated visually and semi-quantitatively using the tumor-to-normal cerebellum ratio (TNR).


In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 ± 0.97 and 1.43 ± 0.42 (p < 0.00001) in group 1, 2.91 ± 0.83 and 1.44 ± 0.20 (p < 0.005) in group 2, and 2.63 ± 1.16 and 1.35 ± 0.23 (p < 0.05) in group 3, respectively. Using a cut-off value of TNR = 1.67, which was calculated by normal reference regions of interest, we could predict necrosis with sensitivity, specificity, and accuracy of 96.7, 93.1, and 94.9 %, respectively.


FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoral micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for treatment decisions or surgical strategies of any type of brain tumor.


Necrosis FMISO PET Hypoxia Brain tumor Biopsy Histology 



The authors thank the staff at the Departments of Nuclear Medicine, Molecular Imaging, Radiology, Neurosurgery, and Cancer Pathology of Hokkaido University Graduate School of Medicine, and Department of Surgical Pathology of Hokkaido University Hospital.

Compliance with Ethical Standards

The authors declare that they have no conflict of interest. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Takuya Toyonaga
    • 1
  • Kenji Hirata
    • 1
  • Shigeru Yamaguchi
    • 1
    • 2
    Email author
  • Kanako C. Hatanaka
    • 3
  • Sayaka Yuzawa
    • 4
  • Osamu Manabe
    • 1
  • Kentaro Kobayashi
    • 1
  • Shiro Watanabe
    • 1
  • Tohru Shiga
    • 1
  • Shunsuke Terasaka
    • 2
  • Hiroyuki Kobayashi
    • 2
  • Yuji Kuge
    • 5
  • Nagara Tamaki
    • 1
  1. 1.Department of Nuclear Medicine, Graduate School of MedicineHokkaido UniversitySapporoJapan
  2. 2.Department of Neurosurgery, Graduate School of MedicineHokkaido UniversitySapporoJapan
  3. 3.Department of Surgical PathologyHokkaido University HospitalSapporoJapan
  4. 4.Department of Cancer Pathology, Graduate School of MedicineHokkaido UniversitySapporoJapan
  5. 5.Central Institute of Isotope ScienceHokkaido UniversitySapporoJapan

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