Change in 18F-Fluoromisonidazole PET Is an Early Predictor of the Prognosis in the Patients with Recurrent High-Grade Glioma Receiving Bevacizumab Treatment

Abstract

BackgroundBevacizumab (BEV), a humanized monoclonal antibody, become a currently important chemotherapeutic option for the patients with recurrent glioma. The aim of this retrospective study is to investigate whether 18F-Fluoromisonidazole (FMISO) PET have the potential to detect BEV-resistant gliomas in the early-stage.MethodsWe reviewed the FMISO PET and MRI appearances before and 3 to 4 courses after BEV treatment on 18 recurrent glioma patients. FMISO accumulation was assessed by visual inspection and semi-quantitative values which were tumor-to-normal (T/N) ratio and hypoxic volume. MRI responses were evaluated based on RANO (Response Assessment in Neuro-Oncology) criteria. The prognostic analysis was performed in relation to the response assessment by FMISO PET and MRI using overall survival (OS) after BEV application.ResultsAfter BEV application, MRI revealed partial response in 14 of 18 patients (78%), of which 9 patients also demonstrated decreased FMISO accumulation. These 9 patients (50%) were classified as “MRI-FMISO double responder”. As for the other 5 patients (28%), FMISO accumulation volumes increased or remained stable after BEV treatment although partial responses were achieved on MRI. Therefore, these cases were classified as “MRI-only responder”. The remaining 4 patients (22%) did not show treatment response on FMISO PET or MRI (“non-responder”). MRI-FMISO double responders showed significantly longer OS than that in other groups (median 12.4 vs 5.7 months; P < 0.001), whereas there were no overall survival difference between MRI-only responders and non-responders (median OS, 5.7 and 4.8 months; P = 0.58). Among the pre-treatment clinical factors, high FMISO T/N ratio was a significant prognostic factor of overall survival in these patients under the assessment of Cox proportional hazard model.ConclusionsRecurrent gliomas with decreasing FMISO accumulation after short-term BEV application could derive a survival benefit from BEV treatment. Change in FMISO PET appearance can identify BEV-resistant gliomas in early-stage regardless of MRI findings in a comprehensible way.

Prediction of Hypoxia in Brain Tumors Using a Multivariate Model Built from MR Imaging and ¹⁸F-Fluorodeoxyglucose Accumulation Data

“…17 18 F-FMISO PET is also thought to be useful for assessment of the response to treatment, such as radiation combined with temozolomide or bevacizumab for high-grade glioma, and for detecting changes in oxygenation, so the prediction map might be suitable for that purpose. 18,19 Although the cerebral cortex and basal ganglia were shown on the prediction map, these areas are easily recognized as normal structures by their shape, and can be excluded when we see a FLAIR image that shows the rough boundary of the tumor.…”

“…18 F-FMISO PET is also thought to be useful for assessment of the response to treatment, such as radiation combined with temozolomide or bevacizumab for high-grade glioma, and for detecting changes in oxygenation, so the prediction map might be suitable for that purpose. 18 , 19 …”

“…An earlier study that investigated the relationship between 18 F-FMISO PET and MRI findings in glioblastoma found that uptake of FMISO was associated with cerebral blood volume in that there was a positive correlation between the extent of hypoxia within a tumor and hypervascularity of the tumor and between maximum 18 F-FMISO uptake and blood volume. 14 It was also suggested that tumor hypoxia and hypervascularization were more frequent and intense in contrast-enhanced areas of glioblastomas that are thought to indicate abnormal vascular permeability zones caused by breakdown of the blood-brain barrier, although Gerstner et al did not perform a quantitative analysis of permeability using DCE in their study.…”

Current Landscape and Emerging Fields of PET Imaging in Patients with Brain Tumors

“…More recently, [ 18 F]FMISO PET has been used for monitoring the effects of antiangiogenic therapy with bevacizumab in patients with recurrent malignant glioma [132,133]. It was shown that patients who had a response in both contrast-enhanced MRI and [ 18 F]FMISO PET had significantly longer survival than patients who responded on MRI only [133].…”

Molecularly targeted therapies in cancer: a guide for the nuclear medicine physician

“…Using Zirkonium-89, the in vivo biodistribution of bevacizumab was shown. In another study the modulation of the hypoxic area within a tumor by bevacizumab was demonstrated by means of a hypoxia PET tracer [ 17 , 117 , 118 ]. Immune Modulation …”