Regional Hypoxia in Glioblastoma Multiforme Quantified with [18F]Fluoromisonidazole Positron Emission Tomography before Radiotherapy: Correlation with Time to Progression and Survival

Spence, Alexander M.; Muzi, Mark; Swanson, Kristin R.; O’Sullivan, Finbarr; Rockhill, Jason K.; Rajendran, Joseph G.; Adamsen, Tom Christian Holm; Link, Jeanne; Swanson, Paul E.; Yagle, Kevin; Rostomily, Robert; Silbergeld, Daniel L.; Krohn, Kenneth A.

doi:10.1158/1078-0432.ccr-07-4995

Cited by 248 publications

(216 citation statements)

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“…In such conditions, glucose is metabolized without consuming oxygen to produce lactate (anaerobic glycolysis) whereas oxygen is essential to fully metabolize glucose (oxidative phosphorylation) [10]. Hypoxia imaging has been reported to provide prognostic information in glioblastoma patients; for example, previous studies found that glioblastoma patients with a larger hypoxia volume (HV) in the tumor had shorter survival [11][12][13][14]. However, hypoxia imaging may reflect not only active tumor cells but also dying cells that could not survive severe hypoxic conditions [8].…”

Section: It Is Defined As Grade IV According To the 2007 World Healthmentioning

confidence: 99%

Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor

Toyonaga

Yamaguchi

Hirata

et al. 2016

Eur J Nucl Med Mol Imaging

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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. 4Results: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.

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Section: It Is Defined As Grade IV According To the 2007 World Healthmentioning

confidence: 99%

Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor

Toyonaga

Yamaguchi

Hirata

et al. 2016

Eur J Nucl Med Mol Imaging

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“…Our results in the first study are consistent with this previous data, except for the grade III patients, as all of our grade III gliomas were FMISO negative. Cher et al used 2 h as the waiting time before conducting the FMISO PET scanning, while the study here used 4 h. Many FMISO PET protocols have used 2 h as the uptake time [24,25,[27][28][29][30][31][32], while Thorwarth et al questioned the adequacy of 2 h for imaging of FMISO [34]. There, the kinetic analysis of dynamic datasets of FMISO PET suggested that the hot spots at 2 h did not reflect actual hypoxia but rather showed a high initial influx of the FMISO due to increased blood flow to the tumor.…”

Section: Discussionmentioning

confidence: 99%

“…In general, the hypoxic volume is distinguished with tissue-to-blood ratios ! 1.2 in images acquired 2 h after FMISO injection with venous blood samples [28][29][30][31]. In brain tumor segmentation for MET PET, a tumor-to-normal ratio !…”

Section: Discussionmentioning

confidence: 99%

“…Early reports by Grunbaum et al [33] and Thorwarth et al [34] addressing this issue suggested a 4-h acquisition as suitable. Despite this, most research adopted 2-h protocols [24,25,[27][28][29][30][31][32], possibly because a shorter protocol would be more generally acceptable in clinical settings. Based on this, the second part of our project was to directly compare 2-h and 4-h images from the same patients [2].…”

Section: Introductionmentioning

confidence: 99%

“…An alternative is presented by 18 F-fluoromisonidazole (FMISO) PET which is a widely used method for in vivo hypoxia imaging [20][21][22][23]. Valk et al first introduced the use of FMISO for glioma imaging in 1992 [24], and the usefulness of FMISO for glioma imaging has been extensively investigated [25][26][27][28][29][30][31][32]. The FMISO is also known to accumulate in severe hypoxic structures but not in mildly hypoxic structures, suggesting that FMISO would be able to discriminate severe from mild hypoxia.…”

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Hypoxia Imaging with 18F-FMISO PET for Brain Tumors

Hirata

Kobayashi

Tamaki

2016

Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy

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Tumor hypoxia is an important object for imaging because hypoxia is associated with tumor aggressiveness and resistance to radiation therapy. Here, 18 Ffluoromisonidazole (FMISO) has been used for many years as the most commonly employed hypoxia imaging tracer. Unlike F-18 fluorodeoxyglucose (FDG), FMISO does not accumulate in normal brain tissue making it able to provide images of hypoxic brain tumors with high contrast. Clinical evidence has suggested that FMISO PET can predict patient prognosis and treatment response. Among gliomas of various grades (WHO 2007), it has been known that grade IV glioblastoma resides under severe hypoxia and is a cause of development of necrosis in the tumor. For this study we tested whether FMISO can distinguish the oxygen condition of glioblastomas and lower-grade gliomas. Twenty-three glioma patients underwent FMISO PET for the study. All the glioblastoma patients (N ¼ 14) showed high FMISO uptakes in the tumor, whereas none of the other patients (i.e., gliomas of grade III or lower, N ¼ 9) did, demonstrated by both qualitative and quantitative assessments. The data suggest that FMISO PET may be a useful tool to distinguish glioblastomas from lower-grade gliomas. Our results, however, were slightly different from previous investigations reporting that some lowergrade gliomas (e.g., grade III) showed positive FMISO uptake. Many of these acquired the FMISO PET images 2 h after the FMISO injection, while for the study here we waited 4 h to be able to collect hypoxia-specific signals rather than perfusion signals as FMISO clearance from plasma is slow due to its lipophilic nature. No optimum uptake time for FMISO has been established, and we directly compared the 2-h vs. the 4-h images with the same patients (N ¼ 17). At 2 h, the gray matter had significantly higher standardized uptake value (SUV) than the white matter, possibly due to different degrees of perfusion but not due to hypoxia. At 4 h, there were no differences between gray and white matter without any significant increase in the noise level measured by the coefficient of variation between the 2-h and the 4-h images. At 2 h, 6/8 (75 %) of glioblastoma patients showed higher uptakes in the tumor than in the surrounding brain tissue, whereas at 4 h this was the case for 8/8 (100 %). In addition, at 2 h, 3/4 (75 %) of patients with lower-grade gliomas showed moderate uptakes, while at 4 h none did (0/4 or 0 %). These data indicate that 4-h images are better than 2-h images for the purpose of glioma grading. In conclusion, we evaluated the diagnostic performance of FMISO PET for gliomas and suggest that FMISO PET may be able to assist in the diagnosis of glioblastomas when PET images are acquired at 4 h post injection.Keywords Hypoxia • 18 F-Fluoromisonidazole • Glioma • Glioblastoma IntroductionThis 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 ...

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Imaging as a predictor of therapeutic response

Mankoff

Shields

2016

Handbook for Clinical Trials of Imaging and Image‐Guided Interventions

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Regional Hypoxia in Glioblastoma Multiforme Quantified with [18F]Fluoromisonidazole Positron Emission Tomography before Radiotherapy: Correlation with Time to Progression and Survival

Cited by 248 publications

References 44 publications

Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor

Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor

Hypoxia Imaging with 18F-FMISO PET for Brain Tumors

Imaging as a predictor of therapeutic response

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