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

Abstract

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 18 F 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 PET for the differential diagnosis of GBM from lower grade gliomas. Methods: This prospective study included 23 patients with pathologically confirmed gliomas. All the patients underwent FMISO PET and FDG PET within a week. FMISO images were acquired 4 hours 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: Thirteen of the 23 glioma patients were diagnosed as having GBM (grade IV glioma in WHO classification 2007), and the others were diagnosed as having non-GBM (5 grade III and 4 grade II). In visual assessment, all the 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 2 from FDG PET study because of hyperglycemia. All the GBM patients and 3 of the 9 (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. 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.

62Cu-Diacetyl-Bis (N4-Methylthiosemicarbazone) PET in Human Gliomas: Comparative Study with [18F]Fluorodeoxyglucose and L-Methyl-[11C]Methionine PET

“…10 Therefore, 62 Cu-ATSM-PET may be a radiotracer useful in the identification of treatment-resistant hypoxic regions in patients with glioma. Our present study also demonstrated that hypoxic imaging by use of 62 Cu-ATSM for discrimination of GBM from non-GBM gliomas may be as effective as [ 18 F]fluoromisonidazole, 12 indicating that hypoxic imaging, including 62 Cu-ATSM, would be a better choice than FDG in the prediction of GBM. However, to our knowledge, correlations between hypoxic regions depicted by PET studies and high-uptake regions in FDG or MET have not been precisely studied in GBM.…”

ERGO: A pilot study of ketogenic diet in recurrent glioblastoma

“…Indeed, there is evidence of HIF-1α and glucose transporter 3 (GLUT3) expression (10) and of increased lactate accumulation in malignant gliomas (11). Further, FDG-PET and 18 F-fluoromisonidazole (FMISO)-PET showed increased glucose uptake and hypoxia in malignant gliomas (12,13). Recently, innovative metabolic flux analyses confirmed increased glucose metabolism in glioblastoma tissue (14) and mouse xenograft tumors (15).…”

Hypoxia Imaging with 18F-FMISO PET for Brain Tumors

“…Twenty-seven patients with possible high-grade gliomas were considered for the study [1]. The patients included showed cerebral parenchymal tumors surrounded by edematous tissue on MR images but no known malignancy in other organs.…”

“…This review article summarizes our recent studies with 18 F-fluoromisonidazole (FMISO) positron emission tomography (PET) applied to brain tumors [1,2]. A variety of tumors which can be divided into two categories develop in the brain: primary brain tumors that originate from the brain tissue and metastatic brain tumors that originate from malignant tumors in other organs.…”

“…If such a difference could be substantiated, hypoxia imaging using FMISO would provide an avenue to discriminate glioblastomas from lower-grade gliomas. The first paper of our project was to test the hypothesis [1]. We evaluated the diagnostic usefulness of FMISO PET in terms of glioma grading in comparison with diagnosis with FDG PET in patients suspected of having glioblastomas on MR images.…”