title: The relationship between endogenous thymidine concentrations and [(18)F]FLT uptake in a range of preclinical tumour models.
abstract: BACKGROUND
  Recent studies have shown that 3'-deoxy-3'-[(18)F] fluorothymidine ([(18)F]FLT)) uptake depends on endogenous tumour thymidine concentration. The purpose of this study was to investigate tumour thymidine concentrations and whether they correlated with [(18)F]FLT uptake across a broad spectrum of murine cancer models. A modified liquid chromatography-mass spectrometry (LC-MS/MS) method was used to determine endogenous thymidine concentrations in plasma and tissues of tumour-bearing and non-tumour bearing mice and rats. Thymidine concentrations were determined in 22 tumour models, including xenografts, syngeneic and spontaneous tumours, from six research centres, and a subset was compared for [(18)F]FLT uptake, described by the maximum and mean tumour-to-liver uptake ratio (TTL) and SUV.
  
  
  RESULTS
  The LC-MS/MS method used to measure thymidine in plasma and tissue was modified to improve sensitivity and reproducibility. Thymidine concentrations determined in the plasma of 7 murine strains and one rat strain were between 0.61 ± 0.12 μM and 2.04 ± 0.64 μM, while the concentrations in 22 tumour models ranged from 0.54 ± 0.17 μM to 20.65 ± 3.65 μM. TTL at 60 min after [(18)F]FLT injection, determined in 14 of the 22 tumour models, ranged from 1.07 ± 0.16 to 5.22 ± 0.83 for the maximum and 0.67 ± 0.17 to 2.10 ± 0.18 for the mean uptake. TTL did not correlate with tumour thymidine concentrations.
  
  
  CONCLUSIONS
  Endogenous tumour thymidine concentrations alone are not predictive of [(18)F]FLT uptake in murine cancer models.
authors: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.|Present address: Comprehensive Cancer Imaging Centre, Imperial College London, London, UK.
authors: Kathrin
authors: K
authors: Heinzmann
authors: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
authors: Davina Jean
authors: DJ
authors: Honess
authors: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.|CRUK-EPSRC Cancer Imaging Centre in Cambridge and Manchester, Cambridge, UK.
authors: David Yestin
authors: DY
authors: Lewis
authors: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
authors: Donna-Michelle
authors: DM
authors: Smith
authors: Wolfson Molecular Imaging Centre, Manchester Pharmacy School, University of Manchester, Manchester, UK.|Present address: Positron Emission Tomography Research Centre, University of Hull, Hull, UK.
authors: Christopher
authors: C
authors: Cawthorne
authors: Personalised Healthcare and Biomarkers, AstraZeneca, Alderley Park, Macclesfield, UK.
authors: Heather
authors: H
authors: Keen
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors: Sandra
authors: S
authors: Heskamp
authors: European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms-Universität (WWU), University Hospital of Münster, Münster, Germany.
authors: Sonja
authors: S
authors: Schelhaas
authors: Comprehensive Cancer Imaging Centre, Imperial College London, London, UK.|Present address: UCL Centre for Advanced Biomedical Imaging, University College London, London, UK.
authors: Timothy Howard
authors: TH
authors: Witney
authors: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.|CRUK-EPSRC Cancer Imaging Centre in Cambridge and Manchester, Cambridge, UK.
authors: Dmitry
authors: D
authors: Soloviev
authors: Wolfson Molecular Imaging Centre, Manchester Pharmacy School, University of Manchester, Manchester, UK.|CRUK-EPSRC Cancer Imaging Centre in Cambridge and Manchester, Cambridge, UK.
authors: Kaye Janine
authors: KJ
authors: Williams
authors: European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms-Universität (WWU), University Hospital of Münster, Münster, Germany.
authors: Andreas Hans
authors: AH
authors: Jacobs
authors: Comprehensive Cancer Imaging Centre, Imperial College London, London, UK.
authors: Eric Ofori
authors: EO
authors: Aboagye
authors: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
authors: John Richard
authors: JR
authors: Griffiths
authors: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK. kmb1001@cam.ac.uk.|CRUK-EPSRC Cancer Imaging Centre in Cambridge and Manchester, Cambridge, UK. kmb1001@cam.ac.uk.|Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK. kmb1001@cam.ac.uk.
authors: Kevin Michael
authors: KM
authors: Brindle
keywords: Plasma; Preclinical PET; Thymidine; Tumour; [18F]Fluorothymidine