Abstract
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Objectives Malignant pleural mesothelioma (MPM) is a chemoresistant cancer with a poor prognosis. Hypoxia is an important factor in tumor aggressiveness and resistance to chemotherapy and radiotherapy. The aim of this pilot study was to determine the activity of the hypoxia imaging agent F-18 fluoromisonidazole (FMISO) using positron emission tomography/computed tomography (PET-CT) in MPM and to compare FMISO activity with glucose metabolism using F-18 fluorodeoxyglucose (FDG).
Methods Consenting patients with histologically or cytologically confirmed MPM not currently receiving systemic or local treatment underwent FMISO and FDG PET-CT scans. Patients received 300 MBq/m2 of FMISO with 2 hour uptake prior to imaging. FDG PET was performed as per standard clinical protocol (6 hour fast, 200 MBq/m2 FDG, 60 minute uptake). FMISO and FDG PET-CT scans were analysed visually and semi-quantitatively by two independent PET physicians. Regions of interest were drawn at sites of maximal tumor activity to obtain FDG and FMISO SUVmax and FMISO tumor to background (muscle) ratio (TBR).
Results 20 patients (19 male, 1 female) were recruited. Visual analysis demonstrated FMISO activity in 17 of 20 patients. One patient with previously treated MPM in remission had no evidence of FDG or FMISO activity and was excluded from semi-quantitative analysis. Overall mean tumor FDG SUVmax was 7.1 (range 1.9 to 19.1) and FMISO SUVmax was 2.4 (range 1.4 to 3.7). Mean TBR in the 17 FMISO positive patients was 1.8 (range 1.2 to 2.5). FDG and FMISO SUVmax values displayed positive correlation (r=0.75, p<0.001).
Conclusions MPM demonstrates evidence of hypoxia on FMISO PET-CT imaging. Tumors exhibiting higher metabolic activity also had more hypoxia. The relationship of hypoxia to treatment response in MPM warrants prospective assessment