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Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor

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Title: Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor
Authors: Toyonaga, Takuya Browse this author
Yamaguchi, Shigeru Browse this author
Hirata, Kenji Browse this author →KAKEN DB
Kobayashi, Kentaro Browse this author
Manabe, Osamu Browse this author →KAKEN DB
Watanabe, Shiro Browse this author
Terasaka, Shunsuke Browse this author →KAKEN DB
Kobayashi, Hiroyuki Browse this author
Hattori, Naoya Browse this author
Shiga, Tohru Browse this author →KAKEN DB
Kuge, Yuji Browse this author →KAKEN DB
Tanaka, Shinya Browse this author →KAKEN DB
Ito, Yoichi M. Browse this author →KAKEN DB
Tamaki, Nagara Browse this author →KAKEN DB
Keywords: Anaerobic glycolysis
Positron emission tomography
Issue Date: Apr-2017
Publisher: Springer
Journal Title: European Journal of Nuclear Medicine and Molecular Imaging
Volume: 44
Issue: 4
Start Page: 611
End Page: 619
Publisher DOI: 10.1007/s00259-016-3541-z
PMID: 27752745
Abstract: Purpose: Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. Experimental Design: Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV × FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. Results: All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV, patients’ age, or Karnofsky performance scale (KPS) was significantly correlated with PSF or OS. The hMTV and hTLG were found to be independent factors affecting PFS and OS on multivariate analysis. Conclusions: We introduced hMTV and hTLG using FDG and FMISO PET to define metabolically active hypoxic volume. Univariate and multivariate analyses demonstrated that both hMTV and hTLG are significant predictors for PFS and OS in glioblastoma patients.
Rights: The final publication is available at
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 豊永 拓哉

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