Characterization of hypoxia in malignant pleural mesothelioma with FMISO PET-CT

Francis, Roslyn J.; Segard, Tatiana; Morandeau, Laurence; Lee, Gary; Millward, Michael; Segal, Amanda; Nowak, Anna K.

doi:10.1016/j.lungcan.2015.07.015

Cited by 30 publications

(22 citation statements)

References 22 publications

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“…Radiotherapy reduced median fractional hypoxic volume from 58 to 22% Eschmann et al [259]FMISO scans performed preradiotherapy in a group of 14 patients with NSCLC: a high TMR and tumour/mediastinal ratio was associated with a higher risk of relapse. FMISO imaging could identify postradiotherapy tumour recurrence due to differential uptake of tracer Cherk et al [155]In 21 patients with NSCLC, low FMISO uptake was seen, with no correlation with FDG uptake and surrogate tissue markers of hypoxia, such as microvessel density and GLUT1 and angiogenesis Gagel et al [260]In 8 patients with NSCLC treated with a combination of chemotherapy and/or radiotherapy, a decrease in FDG and FMISO uptake after treatment was associated with a favourable outcome, and a high initial FMISO uptake was a poor prognostic indicator Vera et al [156]FMISO uptake higher in tumours than in nodes and did not change during therapy Thureau et al [245]Low reproducibility and inter-observer agreement for FMISO volume measurements on the basis of visual assessment Francis et al [222]Visual analysis demonstrated tumour FMISO activity in 17 of 20 patients with malignant mesothelioma. This pilot study confirmed that mesothelioma is a tumour with significant areas of hypoxia, particularly in dominant tumour massesFAZA Bollineni et al [164]FAZA PET is able to detect heterogeneous distributions of hypoxic sub-volumes on visual analysis.…”

Section: Methodsmentioning

confidence: 99%

Molecular mechanisms of hypoxia in cancer

Challapalli¹,

Carroll

Aboagye

2017

Clin Transl Imaging

128

108

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PurposeHypoxia is a condition of insufficient oxygen to support metabolism which occurs when the vascular supply is interrupted, or when a tumour outgrows its vascular supply. It is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. This review provides an overview of hypoxia imaging with Positron emission tomography (PET), with an emphasis on the biological relevance, mechanism of action, highlighting advantages, and limitations of the currently available hypoxia radiotracers.MethodsA comprehensive PubMed literature search was performed, identifying articles relating to biological significance and measurement of hypoxia, MRI methods, and PET imaging of hypoxia in preclinical and clinical settings, up to December 2016.ResultsA variety of approaches have been explored over the years for detecting and monitoring changes in tumour hypoxia, including regional measurements with oxygen electrodes placed under CT guidance, MRI methods that measure either oxygenation or lactate production consequent to hypoxia, different nuclear medicine approaches that utilise imaging agents the accumulation of which is inversely related to oxygen tension, and optical methods. The advantages and disadvantages of these approaches are reviewed, along with individual strategies for validating different imaging methods. PET is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels.ConclusionEven though hypoxia could have significant prognostic and predictive value in the clinic, the best method for hypoxia assessment has in our opinion not been realised.

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Section: Methodsmentioning

confidence: 99%

Molecular mechanisms of hypoxia in cancer

Challapalli¹,

Carroll

Aboagye

2017

Clin Transl Imaging

128

108

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“…FMISO is clinically the most extensively investigated hypoxia PET tracer. Several studies in lung cancer patients have suggested stratification strategies based on FMISO uptake and kinetics [9–12]. The hypothesis is that selective dose painting of putative radioresistant hypoxic tumour sub-volumes, as defined by FMISO PET, may improve locoregional control [13].…”

Section: Introductionmentioning

confidence: 99%

Reproducibility of 18F-fluoromisonidazole intratumour distribution in non-small cell lung cancer

et al. 2016

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BackgroundHypoxic tumours exhibit increased resistance to radiation, chemical, and immune therapies. 18F-fluoromisonidazole (FMISO) positron emission tomography (PET) is a non-invasive, quantitative imaging technique used to evaluate the presence and spatial distribution of tumour hypoxia. To facilitate the use of FMISO PET for identification of individuals likely to benefit from hypoxia-targeted treatments, we investigated the reproducibility of FMISO PET spatiotemporal intratumour distribution in patients with non-small cell lung cancer (NSCLC).MethodsTen patients underwent 18F-fluorodeoxyglucose (FDG) PET/CT scans, followed by two FMISO PET/CT scans 1–2 days apart. Nineteen lesions in total were segmented from co-registered FDG PET image sets. Volumes of interest were also defined on normal contralateral lung and subscapularis muscle. The Pearson correlation coefficient r was calculated for mean standardized uptake values (SUV) within investigated volumes of interest and for voxels within tumour volumes (r TV). The reproducibility of FMISO voxelwise distribution, SUV- and tumour-to-blood ratio (TBR)-derived indices was assessed using correlation and Bland-Altman analyses.ResultsThe SUVmax, SUVmean, TBRmax, and TBRmean were highly correlated (r ≥ 0.87, p < 0.001) and were reproducible to within 10–15 %. The mean r TV was 0.84 ± 0.10. 77 % of voxels identified as hypoxic on one FMISO scan were confirmed as such on the other FMISO scan. Mean voxelwise differences between TBR values as calculated from pooled data including all lesions were 0.9 ± 10.8 %.ConclusionsHigh reproducibility of FMISO intratumour distribution in NSCLC patients was observed, facilitating its use in determining the topology of the hypoxic tumour sub-volumes for dose escalation, in patient stratification strategies for hypoxia-targeted therapies, and in monitoring response to therapeutic interventions.Trial registrationCurrent Controlled Trials NCT02016872

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“…28, 29, 30 Recent studies confirmed that MPM is a tumor with significant hypoxic areas in the dominant tumor masses. 31 …”

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Tissue transglutaminase (TG2) enables survival of human malignant pleural mesothelioma cells in hypoxia

et al. 2017

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Malignant pleural mesothelioma (MPM) is an aggressive tumor linked to environmental/occupational exposure to asbestos, characterized by the presence of significant areas of hypoxia. In this study, we firstly explored the expression and the role of transglutaminase 2 (TG2) in MPM cell adaptation to hypoxia. We demonstrated that cells derived from biphasic MPM express the full-length TG2 variant at higher levels than cells derived from epithelioid MPM and normal mesothelium. We observed a significant induction of TG2 expression and activity when cells from biphasic MPM were grown as a monolayer in chronic hypoxia or packed in spheroids, where the presence of a hypoxic core was demonstrated. We described that the hypoxic induction of TG2 was HIF-2 dependent. Importantly, TGM2-v1 silencing caused a marked and significant reduction of MPM cell viability in hypoxic conditions when compared with normoxia. Notably, a TG2-selective irreversible inhibitor that reacts with the intracellular active form of TG2, but not a non-cell-permeable inhibitor, significantly compromised cell viability in MPM spheroids. Understanding the expression and function of TG2 in the adaptation to the hypoxic environment may provide useful information for novel promising therapeutic options for MPM treatment.

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Characterization of hypoxia in malignant pleural mesothelioma with FMISO PET-CT

Cited by 30 publications

References 22 publications

Molecular mechanisms of hypoxia in cancer

Molecular mechanisms of hypoxia in cancer

Reproducibility of 18F-fluoromisonidazole intratumour distribution in non-small cell lung cancer

Tissue transglutaminase (TG2) enables survival of human malignant pleural mesothelioma cells in hypoxia

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