Abstract
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
Highlights
Hypoxic 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
As the second FMISO PET scan was not acquired for five patients due to their inability to continue (n = 3) or technical reasons (n = 2), ten patients in total were included in the reproducibility analysis (Table 1)
As mismatches between PET and CT scans were identified in two patients (#4 and #9), the co-registrations were modified manually based on the PET images
Summary
Hypoxic 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. 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). 18F-fluoromisonidazole (FMISO) positron emission tomography (PET), a non-invasive imaging technique, presents an attractive alternative [6,7,8]. The hypothesis is that selective dose painting of putative radioresistant hypoxic tumour sub-volumes, as defined by FMISO PET, may improve locoregional control [13]. Despite a number of ongoing hypoxiaimaging trials, quantitative assessment of intratumour distribution of hypoxia-specific PET tracers has yet to be widely implemented in the clinical decision-making process
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