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.
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.
Shibahara
Ichiyo
I
Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
Kumabe
Toshihiro
T
Kanamori
Masayuki
M
Saito
Ryuta
R
Sonoda
Yukihiko
Y
Watanabe
Mika
M
Iwata
Ren
R
Higano
Shuichi
S
Takanami
Kentaro
K
Takai
Yoshihiro
Y
Tominaga
Teiji
T
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
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