Comparison of NaF and FDG PET/CT for Assessment of Treatment Response in Castration-Resistant Prostate Cancers With Osseous Metastases

Abstract

Background Assessment of skeletal metastases response to therapy is highly relevant, but unresolved clinical problem. The main goal of this work was to compare pharmacodynamic responses to therapy assessed with NaF and FDG PET/CT. Materials and Methods Prostate cancer patients with known osseous metastases were treated with Zibotentan (ZD4054) and imaged with combined dynamic NaF/FDG PET/CT prior to therapy (Baseline), after 4 weeks of therapy (Week 4) and after 2 weeks of treatment break (Week 6). Kinetic analysis allowed comparison of voxel-based tracer uptake rate parameter Ki, vasculature parameters K1 (measuring perfusion/permeability) and Vb (measuring vasculature fraction in the tissue) together with standardized uptake values (SUVs). Results Correlations were high for the NaF and FDG peak uptake parameters (Ki and SUV correlations ranged from 0.57 to 0.88) and for vasculature parameters (K1 and Vb correlations ranged from 0.61 to 0.81). Correlation between the NaF and FDG Week 4 Ki responses was low (ρ=0.35, p=0.084), but higher for NaF and FDG Week 6 Ki responses (ρ=0.72, p<0.0001). Correlations for vasculature responses were always low (ρ<0.35). NaF and FDG uptakes in the osseous metastases were spatially dislocated, with overlap in the range from 0% to 80%. Conclusions These results showed that late NaF and FDG uptake responses are consistently correlated, but earlier uptake responses and all vasculature responses can be unrelated. This study also proved that FDG and NaF uptakes are spatially dislocated. Although treatment responses assessed with NaF and FDG may be correlated, using both tracers provides additional information.

Optimizing an 18F-NaF and 18F-FDG cocktail for PET assessment of metastatic castration-resistant prostate cancer

“…In our study, the average ratio of 18 F-NaF and 18 F-FDG SUV and therefore the optimal cocktail composition remained stable with therapy, despite the correlations between the 18 F-NaF and 18 F-FDG uptake responses were not always high [15]. If more effective treatment was applied, the average ratio of 18 F-NaF and 18 F-FDG SUV throughout the therapy may not stay stable.…”

“…Spatial displacement of 18 F-NaF and 18 F-FDG uptakes, which we already reported [15], is highly important in the context of combined 18 F-NaF/ 18 F-FDG cocktail PET/CT imaging because it could alter the visual pattern of combined 18 F-NaF/ 18 F-FDG cocktail PET/CT image if the 18 F-NaF/ 18 F-FDG cocktail composition varied. However, visual patterns in Figure 2 does not change dramatically when changing the 18 F-NaF: 18 F-FDG ratio from 1:8 to 1:2, eventhough the 18 F-NaF and 18 F-FDG SUV images have noticeably different patterns (Figure 1).…”

“…In this work we used clinical data from the clinical study that aimed to determine the pharmacodynamic effects of Zibotetan (ZD4054) on mCRPC patients with the various imaging tools (CT, BS, MRI, 18 F-NaF/ 18 F-FDG PET) [15]. …”

Contemporary approaches for imaging skeletal metastasis

“… 52–54 As a result, 18 F-FDG PET may best be used in conjunction with bone scans and to specifically monitor cancer cell response to treatment. 55–57 …”

PET of Glucose Metabolism and Cellular Proliferation in Prostate Cancer

“…Simoncic et al compared dynamic 18 F-NaF and 18 F-FDG PET/CT for assessment of the response to zibotentan in men with bone metastases from prostate cancer (26). Late (2-wk break after 4 wk of therapy, i.e., wk 6) 18 F-NaF and 18 F-FDG uptake responses were correlated, but earlier uptake responses (4 wk of therapy) were unrelated, suggesting that 18 F-NaF uptake and 18 F-FDG uptake in the setting of response assessment may be spatially disjointed and that these radiotracers may provide complementary information.…”