title: The uptake of 3'-deoxy-3'-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels.
abstract: OBJECTIVE
  The aim of this study was to investigate the role of thymidine kinase 1 (TK1) protein in 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) positron emission tomography (PET) studies.
  
  
  METHODS
  We investigated the in vivo kinetics of [18F]FLT in TK1+/- and TK1-/- L5178Y mouse lymphoma tumours that express different levels of TK1 protein.
  
  
  RESULTS
  [18F]FLT-derived radioactivity, measured by a dedicated small animal PET scanner, increased within the tumours over 60 min. The area under the normalised tumour time-activity curve were significantly higher for the TK1+/- compared with the -/- variant (0.89+/-0.02 vs 0.79+/-0.03 MBq ml(-1) min, P=0.043; n=5 for each tumour type). Ex vivo gamma counting of tissues excised at 60 min p.i. (n=8) also revealed significantly higher tumour [18F]FLT uptake for the TK1+/- variant (6.2+/-0.6 vs 4.6+/-0.4%ID g(-1), P=0.018). The observed differences between the cell lines with respect to [18F]FLT uptake were in keeping with a 48% higher TK1 protein in the TK1+/- tumours versus the -/- variant (P=0.043). On average, there were no differences in ATP levels between the two tumour variants (P=1.00). A positive correlation between [18F]FLT accumulation and TK1 protein levels (r=0.68, P=0.046) was seen. Normalisation of the data for ATP content further improved the correlation (r=0.86, P=0.003).
  
  
  CONCLUSIONS
  This study shows that in vivo [18F]FLT kinetics depend on TK1 protein expression. ATP may be important in realising this effect. Thus, [18F]FLT-PET has the potential to yield specific information on tumour proliferation in diagnostic imaging and therapy monitoring.
authors.affiliation: Molecular Therapy and PET Oncology Research Group, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.
authors.forename: Henryk
authors.initials: H
authors.lastname: Barthel
authors.forename: Meg
authors.initials: M
authors.lastname: Perumal
authors.forename: John
authors.initials: J
authors.lastname: Latigo
authors.forename: Qimin
authors.initials: Q
authors.lastname: He
authors.forename: Frank
authors.initials: F
authors.lastname: Brady
authors.forename: Sajinder K
authors.initials: SK
authors.lastname: Luthra
authors.forename: Pat M
authors.initials: PM
authors.lastname: Price
authors.forename: Eric O
authors.initials: EO
authors.lastname: Aboagye
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015224:Dideoxynucleosides / Q000493:pharmacokinetics*; D008223:Lymphoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013937:Thymidine Kinase / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D014408:Biomarkers, Tumor; D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; D013937:Thymidine Kinase; C092717:thymidine kinase 1; C002854:alovudine