Test–Retest Variability in Lesion SUV and Lesion SUR in ¹⁸F-FDG PET: An Analysis of Data from Two Prospective Multicenter Trials

Abstract

Quantitative assessment of radio- and chemotherapy response with ¹⁸F-FDG whole-body PET has attracted increasing interest in recent years. In most published work, SUV has been used for this purpose. In the context of therapy response assessment, the reliability of lesion SUVs, notably their test–retest stability, thus becomes crucial. However, a recent study demonstrated substantial test–retest variability (TRV) in SUVs. The purpose of the present study was to investigate whether the tumor-to-blood SUV ratio (SUR) can improve TRV in tracer uptake. Methods: 73 patients with advanced non–small cell lung cancer from the prospective multicenter trials ACRIN 6678 ( n = 34) and MK-0646-008 ( n = 39) were included in this study. All patients underwent two ¹⁸F-FDG PET/CT investigations on two different days (time difference, 3.6 ± 2.1 d; range, 1–7 d) before therapy. For each patient, up to 7 tumor lesions were evaluated. For each lesion, SUV _max and SUV _peak were determined. Blood SUV was determined as the mean value of a 3-dimensional aortic region of interest that was delineated on the attenuation CT image and transferred to the PET image. SURs were computed as the ratio of tumor SUV to blood SUV and were uptake time–corrected to 75 min after injection. TRV was quantified as 1.96 multiplied by the root-mean-square deviation of the fractional paired differences in SUV and SUR. The combined effect of blood normalization and uptake time correction was inspected by considering R _TRV (TRV _SUR/TRV _SUV), a ratio reflecting the reduction in the TRV in SUR relative to SUV. R _TRV was correlated with the group-averaged-value difference (δ) in CF _mean (δCF _mean) of the quantity δCF = |CF – 1|, where CF is the numeric factor that converts individual ratios of paired SUVs into corresponding SURs. This correlation analysis was performed by successively increasing a threshold value δCF _min and computing δCF _mean and R _TRV for the remaining subgroup of patients/lesions with δCF ≥ δCF _min. Results: The group-averaged TRV _SUV and TRV _SUR were 32.1 and 29.0, respectively, which correspond to a reduction of variability in SUR by an R _TRV factor of 0.9 in comparison to SUV. This rather marginal improvement can be understood to be a consequence of the atypically low intrasubject variability in blood SUV and uptake time and the accordingly small δCF values in the investigated prospective study groups. In fact, subgroup analysis with increasing δCF _min thresholds revealed a pronounced negative correlation (Spearman ρ = −0.99, P < 0.001) between R _TRV and δCF _mean, where R _TRV ≈ 0.4 in the δCF _min = 20% subgroup, corresponding to a more than 2-fold reduction of TRV _SUR compared with TRV _SUV. Conclusion: Variability in blood SUV and uptake time has been identified as a causal factor in the TRV in lesion SUV. Therefore, TRV in lesion uptake measurements can be reduced by replacing SUV with SUR as the uptake measure. The improvement becomes substantial for the level of variability in blood SUV and uptake time typically observed in the clinical context.