Hypoxia Imaging in Gliomas With 18F-Fluoromisonidazole PET: Toward Clinical Translation

Bell, Christopher J.; Dowson, Nicholas; Fay, Mike; Thomas, Paul; Puttick, Simon; Gal, Yaniv; Rose, Stephen

doi:10.1053/j.semnuclmed.2014.10.001

Cited by 64 publications

(41 citation statements)

References 168 publications

(178 reference statements)

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“…Essentially, as tumour cells proliferate, an insufficient oxygen supply may cause local hypoxia [20]. Even though malignant tumour cells are resistant to such severe circumstances, a fraction of cells would fail to survive and thus undergo necrosis [21].…”

Section: Discussionmentioning

confidence: 99%

18F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors

Toyonaga

Hirata

Yamaguchi

et al. 2016

Eur J Nucl Med Mol Imaging

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2 AbstractPurpose:Tumour necrosis is one of the indicators of tumour aggressiveness.18 F-fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoural necrosis can be detected by FMISO PET in brain tumours regardless of their histopathology. We applied FMISO PET to various types of brain tumours before tumour resection and evaluated the correlation between histopathological necrosis and FMISO uptake. Methods:This study included 59 brain tumour patients who underwent FMISO PET/computed tomography before any treatments.According to the pathological diagnosis, the brain tumours were divided into three groups: astrocytomas (group 1), neuroepithelial tumours except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumour was evaluated visually and semi-quantitatively using the tumour-to-normal cerebellum ratio (TNR). Results:In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 ± 0.97 and 1.43 ± 0.42 (p < 0.00001) in group 1, 2.91 ± 0.83 and 1.44 ± 0.20 (p < 0.005) in group 2, and 2.63 ± 1.16 and 1.35 ± 0.23 (p < 0.05) in group 3, respectively. Using a cut-off value of TNR=1.67, which was calculated by normal reference regions of interest,we could predict necrosis with sensitivity, specificity, and accuracy of 96.7%, 93.1%, and 94.9%, respectively. Conclusions:FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoural micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for treatment decisions or surgical strategies of any type of brain tumour.

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Section: Discussionmentioning

confidence: 99%

18F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors

Toyonaga

Hirata

Yamaguchi

et al. 2016

Eur J Nucl Med Mol Imaging

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“…F-18 fluoromisonidazole (FMISO) positron emission tomography (PET) is the most widely used technique for the localization and quantification of hypoxia in vivo [9], and enables the non-invasive detection of hypoxia in glioblastoma patients [5].…”

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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“…However, due to extensive invasion and rapid proliferation, the survival of GBM patients is only approximately one year (12e14 months), and the 5-year survival rate is only 9.8% at best [3]. For grade II and III gliomas, the prognosis is much better but remains poor, at 2 years and 2e5 years, respectively [4].…”

Section: Introductionmentioning

confidence: 99%