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

Abstract

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.

Influence of the scan time point when assessing hypoxia in 18F-fluoromisonidazole PET: 2 vs. 4 h

“…We also observed a strong relationship between the presence of necrosis and 18 F-FMISO uptake, regardless of the pathological subtype [22]. However, other studies have reported that 18 F-FMISO uptake was observed in not only GBMs but also lower-grade gliomas [12,17,23].…”

Hypoxia imaging and radiotherapy: bridging the resolution gap

“… 62 In the case of glioblastoma, high 18 F-FMISO uptake has been shown as a predictor of micronecrosis in humans. 63 …”

The Roles of Hypoxia Imaging Using 18F-Fluoromisonidazole Positron Emission Tomography in Glioma Treatment

“…Several research groups have compared FMISO uptake with histological findings (such as necrosis and vascularization) and functional features (such as permeability). Our group investigated 59 patients with brain tumors including astrocytic tumors and metastatic tumors, and we examined the presence of microscopic necrosis [50]. In the visual analysis, 26 of the 27 FMISO-positive patients presented with necrosis, whereas 28 of the 32 FMISO-negative patients showed no necrosis.…”