18F-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas
- 632 Downloads
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.
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.
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).
These preliminary data suggest that FMISO PET may distinguish GBM from lower grade gliomas.
KeywordsGlioblastoma multiforme Hypoxia Fluoromisonidazole Fluorodeoxyglucose
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.
- 2.Gorlia T, van den Bent MJ, Hegi ME, Mirimanoff RO, Weller M, Cairncross JG, et al. Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3. Lancet Oncol 2008;9:29–38. doi: 10.1016/S1470-2045(07)70384-4.PubMedCrossRefGoogle Scholar
- 17.Flynn JR, Wang L, Gillespie DL, Stoddard GJ, Reid JK, Owens J, et al. Hypoxia-regulated protein expression, patient characteristics, and preoperative imaging as predictors of survival in adults with glioblastoma multiforme. Cancer 2008;113:1032–42. doi: 10.1002/cncr.23678.PubMedCrossRefGoogle Scholar
- 24.Rajendran JG, Mankoff DA, O’Sullivan F, Peterson LM, Schwartz DL, Conrad EU, et al. Hypoxia and glucose metabolism in malignant tumors: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging. Clin Cancer Res 2004;10:2245–52.PubMedCrossRefGoogle Scholar
- 27.Spence AM, Muzi M, Swanson KR, O’Sullivan F, Rockhill JK, Rajendran JG, et al. Regional hypoxia in glioblastoma multiforme quantified with [18F]fluoromisonidazole positron emission tomography before radiotherapy: correlation with time to progression and survival. Clin Cancer Res 2008;14:2623–30. doi: 10.1158/1078-0432.CCR-07-4995.PubMedCrossRefGoogle Scholar
- 29.Szeto MD, Chakraborty G, Hadley J, Rockne R, Muzi M, Alvord Jr EC, et al. Quantitative metrics of net proliferation and invasion link biological aggressiveness assessed by MRI with hypoxia assessed by FMISO-PET in newly diagnosed glioblastomas. Cancer Res 2009;69:4502–9. doi: 10.1158/0008-5472.CAN-08-3884.PubMedCrossRefGoogle Scholar
- 30.Kawai N, Maeda Y, Kudomi N, Miyake K, Okada M, Yamamoto Y, et al. Correlation of biological aggressiveness assessed by 11C-methionine PET and hypoxic burden assessed by 18F-fluoromisonidazole PET in newly diagnosed glioblastoma. Eur J Nucl Med Mol Imaging 2011;38:441–50. doi: 10.1007/s00259-010-1645-4.PubMedCrossRefGoogle Scholar
- 35.Kracht LW, Miletic H, Busch S, Jacobs AH, Voges J, Hoevels M, et al. Delineation of brain tumor extent with [11C]L-methionine positron emission tomography: local comparison with stereotactic histopathology. Clin Cancer Res 2004;10:7163–70. doi: 10.1158/1078-0432.CCR-04-0262.PubMedCrossRefGoogle Scholar