title: Preclinical dynamic 18F-FDG PET - tumor characterization and radiotherapy response assessment by kinetic compartment analysis.
abstract: BACKGROUND
  Non-invasive visualization of tumor biological and molecular processes of importance to diagnosis and treatment response is likely to be critical in individualized cancer therapy. Since conventional static (18)F-FDG PET with calculation of the semi-quantitative parameter standardized uptake value (SUV) may be subject to many sources of variability, we here present an approach of quantifying the (18)F-FDG uptake by analytic two-tissue compartment modeling, extracting kinetic tumor parameters from dynamic (18)F-FDG PET. Further, we evaluate the potential of such parameters in radiotherapy response assessment.
  
  
  METHODS
  Male, athymic mice with prostate carcinoma xenografts were subjected to dynamic PET either untreated (n=8) or 24 h post-irradiation (7.5 Gy single dose, n=8). After 10 h of fasting, intravenous bolus injections of 10-15 MBq (18)F-FDG were administered and a 1 h dynamic PET scan was performed. 4D emission data were reconstructed using OSEM-MAP, before remote post-processing. Individual arterial input functions were extracted from the image series. Subsequently, tumor (18)F-FDG uptake was fitted voxel-by-voxel to a compartment model, producing kinetic parameter maps.
  
  
  RESULTS
  The kinetic model separated the (18)F-FDG uptake into free and bound tracer and quantified three parameters; forward tracer diffusion (k(1)), backward tracer diffusion (k(2)), and rate of (18)F-FDG phosphorylation, i.e. the glucose metabolism (k(3)). The fitted kinetic model gave a goodness of fit (r(2)) to the observed data ranging from 0.91 to 0.99, and produced parametrical images of all tumors included in the study. Untreated tumors showed homogeneous intra-group median values of all three parameters (k(1), k(2) and k(3)), whereas the parameters significantly increased in the tumors irradiated 24 h prior to (18)F-FDG PET.
  
  
  CONCLUSIONS
  This study demonstrates the feasibility of a two-tissue compartment kinetic analysis of dynamic (18)F-FDG PET images. If validated, extracted parametrical maps might contribute to tumor biological characterization and radiotherapy response assessment.
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo, Norway. Kathrine.Roe@rr-research.no
authors.forename: Kathrine
authors.initials: K
authors.lastname: Røe
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Aleksandersen
authors.forename: Alexandr
authors.initials: A
authors.lastname: Kristian
authors.forename: Line B
authors.initials: LB
authors.lastname: Nilsen
authors.forename: Therese
authors.initials: T
authors.lastname: Seierstad
authors.forename: Hong
authors.initials: H
authors.lastname: Qu
authors.forename: Anne H
authors.initials: AH
authors.lastname: Ree
authors.forename: Dag R
authors.initials: DR
authors.lastname: Olsen
authors.forename: Eirik
authors.initials: E
authors.lastname: Malinen
mesh_terms: D000818:Animals; D001682:Biological Availability; D001825:Body Fluid Compartments / Q000378:metabolism; D005240:Feasibility Studies; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000532:radiotherapy*; D049268:Positron-Emission Tomography / Q000379:methods*; D011379:Prognosis; D014018:Tissue Distribution; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D019788:Fluorodeoxyglucose F18