Timing of hypoxia PET/CT after 18F-Fluoromisonidazole injection in non-small cell lung cancer
Jasmine (Jie Man) Low,
United Kingdom
PO-2078
Abstract
Timing of hypoxia PET/CT after 18F-Fluoromisonidazole injection in non-small cell lung cancer
Authors: Pauline Bourigault1, Jasmine (Jie Man) Low2, Michael Skwarski1,2,3, Ruth Macpherson4, Geoff Higgins1,2, Daniel McGowan1,5
1University of Oxford, Department of Oncology, Oxford, United Kingdom; 2Oxford University Hospitals NHS Foundation Trust, Department of Oncology, Oxford, United Kingdom; 3Guy’s and St Thomas’ NHS Foundation Trust, Department of Clinical Oncology, London, United Kingdom; 4Oxford University Hospitals NHS Foundation Trust, Department of Radiology, Oxford, United Kingdom; 5Oxford University Hospitals NHS Foundation Trust, Department of Medical Physics and Clinical Engineering, Oxford, United Kingdom
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Purpose or Objective
Positron emission tomography (PET)/computed tomography (CT) using the radiotracer 18F-Fluoromisonidazole (FMISO) has been widely employed to image tumour hypoxia and is helpful in guiding radiation treatment (RT) planning. Yet, the optimal timing of hypoxic imaging following 18F-FMISO injection remains unclear in patients with non-small cell lung cancer (NSCLC). Therefore, we investigated the correlation between hypoxia-related quantitative values in FMISO-PET acquired at two- and four-hours post-injection (p.i.) in NSCLC patients.
Material and Methods
Patients with resectable NSCLC were recruited into the ATOM clinical trial (NCT02628080) (1). Cohort 1 (n=14) received atovaquone treatment, while cohort 2 (n=15) did not. Two-hour and four-hour FMISO PET/CT images acquired at baseline and pre-surgery visits (n=58) were compared. Two-hour images were registered to their respective four-hour ones. Spearman’s rank correlation coefficients (ρ) assessed the relationship between hypoxia-related metrics, including standardised uptake value (SUV), tumour-to-blood ratio (TBR), and tumour hypoxic volume (HV) defined by voxels with TBR ≥ 1.4. In-house MATLAB code was used to separate the tumour voxels into four subregions or distance categories: edge (the outermost shell of voxels), outer (voxel centre up to 5.5 mm of the tumour outline), inner (between 5.5 and 11 mm of the tumour outline), and central (superior to 11 mm inside the tumour outline).
Results
In tumours overall, strong correlation (P<0.001) was observed in the following parameters: SUVmax ρ = 0.87, SUVmean ρ = 0.91, TBRmax ρ = 0.83 and TBRmean ρ = 0.81. Tumour HV was moderately correlated (P<0.001) with ρ = 0.69. Yet, in tumour subregions, the correlation of HV decreased from the centre ρ = 0.71 to the edge ρ = 0.45 (P<0.001). Additionally, SUV, TBR, and HV values were higher on four-hour scans than on two-hour scans. For instance, TBRmax mean, median, and interquartile range was 1.9, 1.7, and 1.6-2.0 two hours p.i., and 2.6, 2.4, and 2.0-3.0 four hours p.i., respectively. As the primary imaging-related trial endpoint used to evaluate the action of atovaquone on tumour hypoxia in patients with NSCLC, change in tumour HV from baseline was assessed. Changes in HV in atovaquone-treated patients were relatively similar at two- and four-hours p.i.. However, discrepancies were observed in changes in HV of six (40%) untreated patients, with HV increasing from baseline on four-hour scans while decreasing on two-hour scans, or vice versa.
Conclusion
Given the relatively low tracer-to-background contrast on FMISO-PET images, our results support that scans should be performed at four hours p.i. to evaluate tumour hypoxia in NSCLC, and may better allow hypoxic subvolume definition to potentially guide future RT planning.
Reference:
1. Skwarski, M., et al., Mitochondrial Inhibitor Atovaquone Increases Tumor Oxygenation and Inhibits Hypoxic Gene Expression in Patients with Non-Small Cell Lung Cancer. Clin Cancer Res, 2021. 27(9): p. 2459-2469.