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Background: The standardized uptake value (SUV) is the nearly exclusive means for quantitative evaluation of clinical [18F-]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) whole body investigations. However, the SUV methodology has well known shortcomings. In this context it has been recognized that at least part of the problems can be eliminated if tumor SUV is normalized to the SUV of a reference region in the liver (tumor-to-liver ratio, TLR). In recent publications we have systematically investigated the tumor-to-blood SUV ratio (SUR) for normalization of tumor SUVs which in our view offers principal advantages in comparison to TLR. The aim of this study was a comprehensive comparison of TLR and SUR in terms of quantification of tumor lesions. Methods: 18F-FDG PET/CT was performed in 424 patients (557 scans) with different tumor entities prior to radio(chemo)therapy. In the PET images SUVmax of the primary tumor was determined. SUVliver was calculated in the inferior right lobe of the liver. SUVblood was determined by manually delineating the aorta in the low dose CT. TLR and SUR were computed and scan time corrected to 60min p.i. (TLRtc and SURtc ). Correlation analysis was performed for SUVliver vs. SUVblood , TLR vs. SUR, SUVliver /SUVblood vs. SUVblood , SURtc /TLR vs. SURtc , and SURtc /TLRtc vs. SURtc . Variability of the respective ratios was assessed via histogram analysis. The prognostic value of TLR and TLRtc for distant metastases-free survival (DM) was investigated with univariate Cox regression in a homogeneous subgroup (N=130) and compared to previously published results for SUV and SURtc . Results: Correlation analysis revealed a linear correlation of SUVliver vs. SUVblood (R2 =0.83) and of TLR vs. SURtc (R2 =0.92). The SUVliver /SUVblood ratio (mean ± s.d.) was 1.47±0.18. For the SURtc /TLR ratio we obtained 1.14±0.21 and for the SURtc /TLRtc ratio 1.38±0.17. Survival analysis revealed TLR and TLRtc as significant prognostic factors for DM (hazard ratio (HR)=3.3 and HR=3, respectively). Both hazard ratios are lower than that of SURtc (HR=4.1) although this reduction does not reach statistical significance for the given limited group size. HRs of TLR and SURtc are both significantly higher than HR of SUV (HR=2.2). Conclusion: Suitability of the liver as surrogate of arterial tracer supply for SUV normalization via TLR computation is limited. Further studies in sufficiently large patient groups are required to better characterize the relative performance of SUV, TLR, and SUR in different settings.

The Standard Uptake Value (SUV) approach in oncological PET has known shortcomings all of which affect the reliability of the SUV as a surrogate of the targeted quantity, the metabolic rate of FDG ([18F]fluorodeoxyglucose), Km. Among the shortcomings are time dependence, susceptibility to errors in scanner and dose calibration, insufficient correlation between systemic distribution volume and body weight, and, consequentially, residual inter-study variability of the arterial input function (AIF) despite SUV normalization. Especially the latter turns out to be a crucial factor adversely affecting the correlation between SUV and Km and causing inter-study variations of tumor SUVs that do not reflect actual changes of the metabolic uptake rate. In this work, we propose to replace tumor SUV by the tumor to blood standard uptake ratio (SUR) in order to distinctly improve the linear correlation with Km. Methods: Assuming irreversible FDG kinetics, SUR can be expected to exhibit a much better linear correlation to Km than SUV. The theoretical derivation for this prediction is given and evaluated in a group of 9 patients with liver metastases of colorectal cancer for which 15 fully dynamic investigations were available and Km could thus be derived from conventional Patlak analysis. Results: For any fixed time point T at sufficiently late times p.i. the Patlak equation predicts a linear correlation between SUR and Km under the following assumptions: 1.) approximate shapeinvariance (but arbitrary scale) of the AIF across scans/patients and 2.) low variability of the apparent distribution volume Vr (the intercept of the Patlak Plot). This prediction – and validity of the underlying assumptions – has been verified in the investigated patient group. Replacing tumor SUVs by SURs does improve the linear correlation of the respective parameter with Km from r = 0:61 to r = 0:98. Conclusion: SUR is an easily measurable parameter that is highly correlated to Km. In this respect it is clearly superior to SUV. Therefore, SUR should be seriously considered as a drop-in replacement for SUV-based approaches.