In Vivo Evaluation of FLETT as a Novel PET Imaging Reagent in Tumour Xenografts

  • Dr John Sachinidis, Centre for PET, Austin Hospital, Melbourne, Australia
  • Uwe Ackermann, Centre for PET and The University of Melbourne, Austin Hospital, Melbourne, Australia
  • Glenn Cartwright, Ludwig Institute for Cancer Research, Austin Hospital, Melbourne, Australia
  • Dr Graeme O'Keefe, Centre for PET, Austin Hospital, Melbourne, Australia
  • Dr Sze Ting Lee, Centre for PET and Ludwig Institute for Cancer Research, Austin Hospital, Melbourne, Australia
  • Henri Tochon-Danguy, Centre for PET, Ludwig Institute for Cancer Research and The University of Melbourne, Austin Hospital, Melbourne, Australia
  • Angela Rigopoulos, Ludwig Institute for Cancer Research, Austin Hospital, Melbourne, Australia
  • Diana Cao, Ludwig Institute for Cancer Research, Austin Hospital, Melbourne, Australia
  • Ms Amanda Byrne, Centre for PET, Austin Hospital, Australia
  • A/Prof Damien Bolton, Department of Surgery & Urology, University of Melbourne, Austin Hospital, Victoria, Australia
  • A/Prof Ian Davis, Ludwig Oncology Unit, Austin Hospital, Victoria, Australia
  • Dr Andrew Scott, Austin Health, Ludwig Institute for Cancer Research, University of Melbourne, Australia
  • SS Poniger, Centre for PET, Austin Hospital, Australia

    • Imaging techniques such as PET are proving to be sensitive and specific tools for the diagnosis, monitoring and subsequent management of cancer. Tumour metabolism of glucose and thymidine through the use of 18F-fluoro-2-deoxy-D-glucose (FDG) and 18F-3'-fluoro-3'-deoxy-L-thymidine (FLT) have been used extensively to study tumour growth and DNA synthesis respectively.
    In this study we have developed a simplified synthesis method of the thymidine compound 18F-fluoroethyl triazolyl thymidine (18F-FLETT) using “click chemistry” and the subsequent evaluation of 18F-FLETT in vivo in comparison with 18F-FLT. 18F-Fluoroethyl azide was distilled into a reaction vessel and reacted with ethynyl deoxy uridine to form FLETT. This method has resulted in an increase in overall radiochemical yield from 3% to 25%.
    Small animal PET imaging of A431 xenografts demonstrated peak uptake of 18F-FLETT at 60 mins post injection, and no evidence of bone uptake after 3 hours post injection. These results indicate that the fluoroethyl triazolyl moiety is stable and there is no defluorination in-vivo.
    In conclusion, we have developed a novel synthesis method for 18F-FLETT, and confirmed specific uptake in xenotransplanted nude mice with small animal PET imaging. Further studies to evaluate the biologic relevance of 18F-FLETT imaging in tumours are ongoing.