title: Comparison of the pharmacokinetics of 68Ga-DOTATOC and [18F]FDG in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy.
abstract: OBJECTIVE
  The purpose of this study was to evaluate and compare, by means of dynamic PET, the pharmacokinetics of 68Ga-DOTATOC, a tracer which reflects the expression of somatostatin receptors (SSTRs), and of [18F]FDG, a marker of tumour viability, in patients with metastatic neuroendocrine tumours (NETs) in whom 90Y-DOTATOC therapy was planned.
  
  
  METHODS
  Fifteen patients (63 lesions) with confirmed metastatic NETs were enrolled in this study. Dynamic [18F]FDG and 68Ga-DOTATOC PET scans were performed on two different days in the same week. The data analysis was based on qualitative and quantitative analysis using a two-tissue compartment model with a blood compartment and a non-compartment model based on the fractal dimension (FD). Multivariate analysis was used for evaluation of the kinetic data.
  
  
  RESULTS
  Enhanced [18F]FDG uptake was observed in 43/63 lesions. 68Ga-DOTATOC showed pathologically enhanced uptake in all evaluated patients and in 57/63 lesions. Discordant scintigraphic results for [18F]FDG and 68Ga-DOTATOC were observed in 6/15 patients. Global SUV was defined as the SUV measured in the last frame (55-60 min p.i.) of the dynamic series, for each tracer. The median global SUV uptake was 7.9 for 68Ga-DOTATOC and 4.6 for [18F]FDG. The selection of patients for 90Y-DOTATOC therapy was based on the uptake of 68Ga-DOTATOC. Multiple linear regression analysis was applied to determine the effect of each kinetic parameter (K1-k4, VB) on the global SUV of both tracers. The highest positive t-ratio was found for K1 (receptor binding), followed by k3 (cellular internalisation) and VB (fractional blood volume), when using the global 68Ga-DOTATOC uptake (SUV) as a target variable. Analysis of the [18F]FDG data revealed the highest positive t-ratio for VB, followed by k3 (phosphorylation) and K1 (influx). The comparison of global SUV, K1-k4 and the FD for [18F]FDG and 68Ga-DOTATOC did not show any statistically significant correlation. The only parameter that demonstrated a significant linear correlation between the tracers was VB.
  
  
  CONCLUSIONS
  68Ga-DOTATOC is a promising tool for evaluation of the expression of SSTR2 in NETs. The combination of [18F]FDG and 68Ga-DOTATOC dynamic PET studies provides different information regarding the biological properties of lesions in patients with metastatic NETs in whom 90Y-DOTATOC therapy is planned. While the global 68Ga-DOTATOC uptake is influenced mostly by K1, the global [18F]FDG uptake is mostly influenced by VB. Only patients with enhanced 68Ga-DOTATOC uptake (SUV >5.0) were referred to 90Y-DOTATOC therapy.
authors.affiliation: Medical PET Group-Biological Imaging (E0601), Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: Koukouraki
authors.forename: Ludwig G
authors.initials: LG
authors.lastname: Strauss
authors.forename: Vassilios
authors.initials: V
authors.lastname: Georgoulias
authors.forename: Michael
authors.initials: M
authors.lastname: Eisenhut
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
authors.forename: Antonia
authors.initials: A
authors.lastname: Dimitrakopoulou-Strauss
mesh_terms: D000328:Adult; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy / Q000556:secondary*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D011379:Prognosis; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: C499142:Ga(III)-DOTATOC; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C496730:90Y-octreotide, DOTA-Tyr(3)-; D015282:Octreotide