title: (18)F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors.
abstract: OBJECTIVE
  Tumor necrosis is one of the indicators of tumor aggressiveness. (18)F-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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-Ku, Sapporo, 060-8638, Japan.
authors: Takuya
authors: T
authors: Toyonaga
authors: Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-Ku, Sapporo, 060-8638, Japan.
authors: Kenji
authors: K
authors: Hirata
authors: Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-Ku, Sapporo, 060-8638, Japan. yama-shu@med.hokudai.ac.jp.|Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. yama-shu@med.hokudai.ac.jp.
authors: Shigeru
authors: S
authors: Yamaguchi
authors: Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan.
authors: Kanako C
authors: KC
authors: Hatanaka
authors: Department of Cancer Pathology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors: Sayaka
authors: S
authors: Yuzawa
authors: Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-Ku, Sapporo, 060-8638, Japan.
authors: Osamu
authors: O
authors: Manabe
authors: Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-Ku, Sapporo, 060-8638, Japan.
authors: Kentaro
authors: K
authors: Kobayashi
authors: Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-Ku, Sapporo, 060-8638, Japan.
authors: Shiro
authors: S
authors: Watanabe
authors: Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-Ku, Sapporo, 060-8638, Japan.
authors: Tohru
authors: T
authors: Shiga
authors: Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors: Shunsuke
authors: S
authors: Terasaka
authors: Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors: Hiroyuki
authors: H
authors: Kobayashi
authors: Central Institute of Isotope Science, Hokkaido University, Sapporo, Japan.
authors: Yuji
authors: Y
authors: Kuge
authors: Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-Ku, Sapporo, 060-8638, Japan.
authors: Nagara
authors: N
authors: Tamaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives*; D009336:Necrosis; D049268:Positron-Emission Tomography
chemical_list: C031843:fluoromisonidazole; D008920:Misonidazole
keywords: Biopsy; Brain tumor; FMISO PET; Histology; Hypoxia; Necrosis