Reproducibility of18F-fluoromisonidazole intratumour distribution in non-small cell lung cancer.
BACKGROUND
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. 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).


METHODS
Ten patients underwent18F-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 (rTV). The reproducibility of FMISO voxelwise distribution, SUV- and tumour-to-blood ratio (TBR)-derived indices was assessed using correlation and Bland-Altman analyses.


RESULTS
The SUVmax, SUVmean, TBRmax, and TBRmeanwere highly correlated (r ≥ 0.87, p < 0.001) and were reproducible to within 10-15 %. The mean rTVwas 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 %.


CONCLUSIONS
High 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.


BACKGROUND
Current Controlled Trials NCT02016872.
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. grkovskm@mkscc.org.
Milan
http://orcid.org/0000-0001-7228-9497
M
Grkovski
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
Jazmin
J
Schwartz
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Andreas
A
Rimner
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Heiko
H
Schöder
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Sean D
SD
Carlin
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
Pat B
PB
Zanzonico
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
John L
JL
Humm
National Center for Cancer Care and Research, Doha, Qatar.
Sadek A
SA
Nehmeh
18F-fluoromisonidazole; Hypoxia; Non-small cell lung cancer; Quantification; Reproducibility