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18F-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and its prognosis is significantly poorer than those of less malignant gliomas. Pathologically, necrosis is one of the most important characteristics that differentiate GBM from lower grade gliomas; therefore, we hypothesized that 18F fluoromisonidazole (FMISO), a radiotracer for hypoxia imaging, accumulates in GBM but not in lower grade gliomas. We aimed to evaluate the diagnostic value of FMISO positron emission tomography (PET) for the differential diagnosis of GBM from lower grade gliomas.

Methods

This prospective study included 23 patients with pathologically confirmed gliomas. All of the patients underwent FMISO PET and 18F-fluorodeoxyglucose (FDG) PET within a week. FMISO images were acquired 4 h after intravenous administration of 400 MBq of FMISO. Tracer uptake in the tumor was visually assessed. Lesion to normal tissue ratios and FMISO uptake volume were calculated.

Results

Of the 23 glioma patients, 14 were diagnosed as having GBM (grade IV glioma in the 2007 WHO classification), and the others were diagnosed as having non-GBM (5 grade III and 4 grade II). In visual assessment, all GBM patients showed FMISO uptake in the tumor greater than that in the surrounding brain tissues, whereas all the non-GBM patients showed FMISO uptake in the tumor equal to that in the surrounding brain tissues (p ≤ 0.001). One GBM patient was excluded from FDG PET study because of hyperglycemia. All GBM patients and three of the nine (33%) non-GBM patients showed FDG uptake greater than or equal to that in the gray matter. The sensitivity and specificity for diagnosing GBM were 100 and 100% for FMISO, and 100 and 66% for FDG, respectively. The lesion to cerebellum ratio of FMISO uptake was higher in GBM patients (2.74 ± 0.60, range 1.71–3.81) than in non-GBM patients (1.22 ± 0.06, range 1.09–1.29, p ≤ 0.001) with no overlap between the groups. The lesion to gray matter ratio of FDG was also higher in GBM patients (1.46 ± 0.75, range 0.91–3.79) than in non-GBM patients (1.07 ± 0.62, range 0.66–2.95, p ≤ 0.05); however, overlap of the ranges did not allow clear differentiation between GBM and non-GBM. The uptake volume of FMISO was larger in GBM (27.18 ± 10.46%, range 14.02–46.67%) than in non-GBM (6.07 ± 2.50%, range 2.12–9.22%, p ≤ 0.001).

Conclusion

These preliminary data suggest that FMISO PET may distinguish GBM from lower grade gliomas.

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Acknowledgments

The authors would like to thank the staff of the Department of Nuclear Medicine, Central Institute of Isotope Science, and Department of Cancer Pathology, Hokkaido University, and Department of Radiology, Hokkaido University Hospital for supporting this work.

Sources of funding

This study was performed through Special Coordination Funds for Promoting Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology of Japan. This research was also supported in part by a Grant-in-Aid for General Scientific Research from the Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan

    Kenji Hirata, Tohru Shiga & Nagara Tamaki

  2. Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Shunsuke Terasaka, Hiroyuki Kobayashi, Shigeru Yamaguchi & Kiyohiro Houkin

  3. Department of Molecular Imaging, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Naoya Hattori

  4. Department of Radiology, Hokkaido University Hospital, Sapporo, Japan

    Keiichi Magota

  5. Department of Cancer Pathology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Shinya Tanaka

  6. Central Institute of Isotope Science, Hokkaido University, Sapporo, Japan

    Yuji Kuge

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  1. Kenji Hirata
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Correspondence to Kenji Hirata.

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Hirata, K., Terasaka, S., Shiga, T. et al. 18F-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas. Eur J Nucl Med Mol Imaging 39, 760–770 (2012). https://doi.org/10.1007/s00259-011-2037-0

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