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 a highly relevant but unresolved clinical problem. The main goal of this work was to compare pharmacodynamic responses to therapy assessed with positron emission tomography-computed tomography (PET/CT) using fluorine-18 sodium fluoride (NaF) and fluorine-18 fluorodeoxyglucose (FDG) as the tracers.

Materials and methods: Patients with prostate cancer with known osseous metastases were treated with zibotentan (ZD4054) and imaged with combined dynamic NaF/FDG PET/CT before therapy (baseline), after 4 weeks of therapy (week 4), and after 2 weeks of treatment break (week 6). Kinetic analysis allowed comparison of the voxel-based tracer uptake rate parameter Ki, the vasculature parameters K1 (measuring perfusion/permeability) and Vb (measuring vasculature fraction in the tissue), and the 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 was low between the NaF and FDG week 4 Ki responses (ρ = 0.35; P = .084) but was higher for NaF and FDG week 6 Ki responses (ρ = 0.72; P < .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%.

Conclusion: This study found that late NaF and FDG uptake responses are consistently correlated but that earlier uptake responses and all vasculature responses can be unrelated. This study also confirmed 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.

Trial registration: ClinicalTrials.gov NCT01119118.

Keywords: Dual-tracer PET imaging; Kinetic analysis; Skeletal metastases; Therapy response assessment; Zibotentan.

Figure 1

Schematic representation of the combined NaF/FDG PET/CT image acquisition. Dynamic NaF PET/CT image was constructed from coregistered first PET/CT scan (dynamic scan over one 15 cm segment), second PET/CT scan (whole-body scan) and third PET/CT scan (one-frame scan over 15 cm segment). Dynamic FDG PET/CT scan was constructed by subtracting the NaF baseline activity (obtained by extrapolating the dynamic NaF PET/CT scan) from the fourth PET/CT scan.

Figure 2

Correlation plots for NaF and FDG peak SUV. Each graph is for all the lesions of single patients; four patients had multiple lesions in the FOV. Graphs have added correlation coefficient (ρ) and slope of plotted line that was determined as the average ratio of NaF:FDG SUV.

Figure 3

Correlation plot of NaF and FDG K_i responses. Figure presents NaF versus FDG Week 4 K_i responses (a), NaF versus FDG Week 6 K_i responses (b), and NaF versus FDG K_i changes from Week 4 to Week 6 (c).

Figure 4

Correlation plot of non-equivalent NaF and FDG K_i responses. Figure presents NaF Week 4 K_iresponses versus FDG Week 6 K_i responses (a), NaF Week 6 K_i responses versus FDG Week 4 K_i responses (b), NaF Week 4 K_i responses versus FDG changes from Week 4 to Week 6 (c).

Figure 5

An example of NaF, FDG and combined K_i parametric images, where the areas of high NaF and high FDG uptakes were notably dislocated. Arrows point on the lesions with most notable dislocation between the NaF and FDG uptake.

Figure 6

An example of NaF, FDG and combined K_i parametric images, where the areas of high NaF and high FDG uptakes were less dislocated. Arrows point on the visible lesions with the concordant NaF and FDG uptake.

Figure 7

The concordance of NaF and FDG segmentations for the investigated metastases through the course of therapy.