title: An evaluation of 2-deoxy-2-[18F]fluoro-D-glucose and 3'-deoxy-3'-[18F]-fluorothymidine uptake in human tumor xenograft models.
abstract: OBJECTIVE
  The aim of this study is to assess the variability of 2-deoxy-2-[(18)F]fluoro-D: -glucose ([(18)F]-FDG) and 3'-deoxy-3'-[(18)F]-fluorothymidine ([(18)F]-FLT) uptake in pre-clinical tumor models and examine the relationship between imaging data and related histological biomarkers.
  
  
  METHODS
  [(18)F]-FDG and [(18)F]-FLT studies were carried out in nine human tumor xenograft models in mice. A selection of the models underwent histological analysis for endpoints relevant to radiotracer uptake. Comparisons were made between in vitro uptake, in vivo imaging, and ex vivo histopathology data using quantitative and semi-quantitative analysis.
  
  
  RESULTS
  In vitro data revealed that [1-(14)C]-2-deoxy-D: -glucose ([(14)C]-2DG) uptake in the tumor cell lines was variable. In vivo, [(18)F]-FDG and [(18)F]-FLT uptake was highly variable across tumor types and uptake of one tracer was not predictive for the other. [(14)C]-2DG uptake in vitro did not predict for [(18)F]-FDG uptake in vivo. [(18)F]-FDG SUV was inversely proportional to Ki67 and necrosis levels and positively correlated with HKI. [(18)F]-FLT uptake positively correlated with Ki67 and TK1.
  
  
  CONCLUSIONS
  When evaluating imaging biomarkers in response to therapy, the choice of tumor model should take into account in vivo baseline radiotracer uptake, which can vary significantly between models.
authors.affiliation: PHB Imaging Group, AstraZeneca, 19F22 Mereside, Alderley Park, Macclesfield, SK10 4TG, UK. Heather.Keen@astrazeneca.com
authors.forename: Heather
authors.initials: H
authors.lastname: Keen
authors.forename: Bernd
authors.initials: B
authors.lastname: Pichler
authors.forename: Damaris
authors.initials: D
authors.lastname: Kukuk
authors.forename: Olivier
authors.initials: O
authors.lastname: Duchamp
authors.forename: Olivier
authors.initials: O
authors.lastname: Raguin
authors.forename: Aoife
authors.initials: A
authors.lastname: Shannon
authors.forename: Nichola
authors.initials: N
authors.lastname: Whalley
authors.forename: Vivien
authors.initials: V
authors.lastname: Jacobs
authors.forename: Juliana
authors.initials: J
authors.lastname: Bales
authors.forename: Neill
authors.initials: N
authors.lastname: Gingles
authors.forename: Sally-Ann
authors.initials: SA
authors.lastname: Ricketts
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wedge
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D015224:Dideoxynucleosides / Q000493:pharmacokinetics*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006651:Histocytochemistry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D049268:Positron-Emission Tomography; D012107:Research Design; D014183:Transplantation, Heterologous; D051598:Whole Body Imaging
chemical_list: D014408:Biomarkers, Tumor; D015224:Dideoxynucleosides; D019788:Fluorodeoxyglucose F18; C002854:alovudine