title: Imaging of hypoxic lesions in patients with gliomas by using positron emission tomography with 1-(2-[18F] fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole, a new 18F-labeled 2-nitroimidazole analog.
abstract: OBJECTIVE
  Assessment of hypoxic conditions in brain tumors is important for predicting tumor aggressiveness and treatment response. A new hypoxia imaging agent, 1-(2-[(18)F]fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole (FRP-170), with higher image contrast and faster clearance than preexisting hypoxia tracers for PET, was used to visualize hypoxic tissues in 8 patients with glioma.
  
  
  METHODS
  The FRP-170 was injected and PET imaging was performed 2 hours later in 8 patients, including 3 with glioblastoma multiforme, 2 with oligodendroglioma, and 1 each with diffuse astrocytoma, anaplastic ganglioglioma, and recurrent anaplastic astrocytoma. All 8 patients also underwent MR imaging, and some patients underwent [(11)C]methionine or [(18)F]fluorodeoxyglucose PET, and proton MR spectroscopy for comparison. Tissues obtained at biopsy or radical resection were immunostained with hypoxia-inducible factor-1alpha (HIF-1alpha) antibody for the confirmation of hypoxia, except in the patient with recurrent anaplastic astrocytoma who was treated using Gamma Knife surgery.
  
  
  RESULTS
  The FRP-170 PET images showed marked uptake with upregulation of HIF-1alpha in the 3 glioblastomas multiforme, and moderate uptake in the recurrent anaplastic astrocytoma and one oligodendroglioma, but no uptake in the other tumors. The FRP-170 PET images showed positive correlation with HIF-1alpha immunoreactivity and some correlation with FDG PET and MR imaging enhancement, but no correlation with [(11)C]methionine PET. Imaging with FRP-170 PET seemed to be more sensitive for detecting hypoxia than identifying the lactate peak on proton MR spectroscopy.
  
  
  CONCLUSIONS
  Imaging with FRP-170 PET can visualize hypoxic lesions in patients with glioma, as confirmed by histological examination. This new method can assess tumor hypoxia preoperatively and noninvasively.
authors.affiliation: Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Ichiyo
authors.initials: I
authors.lastname: Shibahara
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kumabe
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kanamori
authors.forename: Ryuta
authors.initials: R
authors.lastname: Saito
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sonoda
authors.forename: Mika
authors.initials: M
authors.lastname: Watanabe
authors.forename: Ren
authors.initials: R
authors.lastname: Iwata
authors.forename: Shuichi
authors.initials: S
authors.lastname: Higano
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takanami
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takai
authors.forename: Teiji
authors.initials: T
authors.lastname: Tominaga
mesh_terms: D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000000981:diagnostic imaging / Q000473:pathology; D001706:Biopsy; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D002247:Carbon Isotopes; D002455:Cell Division; D005260:Female; D019788:Fluorodeoxyglucose F18; D005909:Glioblastoma / Q000000981:diagnostic imaging*; D006801:Humans; D002534:Hypoxia, Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008715:Methionine; D008875:Middle Aged; D009593:Nitroimidazoles; D009837:Oligodendroglioma / Q000000981:diagnostic imaging / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods*; D011522:Protons; D019275:Radiopharmaceuticals
chemical_list: D002247:Carbon Isotopes; C501635:FRP-170; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009593:Nitroimidazoles; D011522:Protons; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D008715:Methionine