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

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. 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. 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. 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.