title: An investigation of the relation between tumor-to-liver ratio (TLR) and tumor-to-blood standard uptake ratio (SUR) in oncological FDG PET.
abstract: 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 [TLR] ratio). 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 60 min 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 (R (2)=0.83) and of TLR vs. SURtc (R (2)=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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, PET Center, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstraße, Dresden, Germany. hofheinz@hzdr.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Hofheinz
authors.affiliation: Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany. Rebecca.Buetof@uniklinikum-dresden.de.|OncoRay - National Center for Radiation Research in Oncology, Dresden, Germany. Rebecca.Buetof@uniklinikum-dresden.de.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bütof
authors.affiliation: Klinik für Radiologie und Nuklearmedizin, Universitätsklinikum Magdeburg A.ö.R., Magdeburg, Germany. ivayla.apostolova@med.ovgu.de.
authors.forename: Ivayla
authors.initials: I
authors.lastname: Apostolova
authors.affiliation: OncoRay - National Center for Radiation Research in Oncology, Dresden, Germany. Klaus.Zoephel@uniklinikum-dresden.de.|Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany. Klaus.Zoephel@uniklinikum-dresden.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Zöphel
authors.affiliation: Klinik für Radiologie und Nuklearmedizin, Universitätsklinikum Magdeburg A.ö.R., Magdeburg, Germany. ingo.steffen@med.ovgu.de.
authors.forename: Ingo G
authors.initials: IG
authors.lastname: Steffen
authors.affiliation: Klinik für Radiologie und Nuklearmedizin, Universitätsklinikum Magdeburg A.ö.R., Magdeburg, Germany. holger.amthauer@med.ovgu.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Amthauer
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, PET Center, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstraße, Dresden, Germany. Joerg.Kotzerke@uniklinikum-dresden.de.|Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany. Joerg.Kotzerke@uniklinikum-dresden.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kotzerke
authors.affiliation: Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany. Michael.Baumann@uniklinikum-dresden.de.|OncoRay - National Center for Radiation Research in Oncology, Dresden, Germany. Michael.Baumann@uniklinikum-dresden.de.|German Cancer Consortium (DKTK), Dresden, Germany. Michael.Baumann@uniklinikum-dresden.de.|German Cancer Research Center (DKFZ), Heidelberg, Germany. Michael.Baumann@uniklinikum-dresden.de.|Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology, Dresden, Germany. Michael.Baumann@uniklinikum-dresden.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Baumann
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, PET Center, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstraße, Dresden, Germany. j.van_den_hoff@hzdr.de.|Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany. j.van_den_hoff@hzdr.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: van den Hoff
keywords: FDG; PET; SUR; TLR; Tumor-to-blood ratio; Tumor-to-liver ratio