In vivo evaluation of 5-[(18)F]fluoro-2'-deoxyuridine as tracer for positron emission tomography in a murine pancreatic cancer model

Cancer Res. 2001 May 15;61(10):3853-7.

Abstract

We used a murine tumor progression model for the evaluation of potential proliferation markers using positron emission tomography (PET). 5-[(18)F]-2'-deoxyuridine ([(18)F]FdUrd) was synthesized with >98% radiochemical purity and investigated in a pancreatic cancer model, transforming growth factor alpha transgenic mice crossbred to p53 deficient mice. Thymidylate synthase was increased already in premalignant lesions, whereas thymidine kinase 1 mRNA levels were up-regulated 4-fold in the pancreatic cancer specimen of these mice. PET imaging was performed after injection of 1 MBq of [(18)F]FdUrd and 1 MBq of [(18)F]fluoro-deoxyglucose. Animals with pancreatic cancer displayed focal uptake of both tracers. The [(18)F]FdUrd uptake ratio closely correlated with the proliferation index as evaluated in morphometric and fluorescence-activated cell sorter analysis. These results indicate the potential of our tumor model for the evaluation of PET tracers and suggest [(18)F]FdUrd as a tracer for the assessment of proliferation in vivo.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Cell Division / physiology
  • Disease Models, Animal
  • Disease Progression
  • Floxuridine* / chemical synthesis
  • Floxuridine* / pharmacokinetics
  • Fluorodeoxyglucose F18
  • Genes, p53 / genetics
  • Mice
  • Mice, Transgenic
  • Pancreatic Neoplasms / diagnostic imaging*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Radionuclide Imaging
  • Radiopharmaceuticals* / chemical synthesis
  • Radiopharmaceuticals* / pharmacokinetics
  • Thymidine Kinase / biosynthesis
  • Thymidine Kinase / genetics
  • Thymidylate Synthase / biosynthesis
  • Thymidylate Synthase / genetics
  • Transforming Growth Factor alpha / genetics
  • Up-Regulation

Substances

  • RNA, Messenger
  • Radiopharmaceuticals
  • Transforming Growth Factor alpha
  • Floxuridine
  • Fluorodeoxyglucose F18
  • Thymidylate Synthase
  • Thymidine Kinase
  • thymidine kinase 1