Synthesis and evaluation of [18F] labeled pyrimidine nucleosides for positron emission tomography imaging of herpes simplex virus 1 thymidine kinase gene expression

J Med Chem. 2006 Aug 24;49(17):5377-81. doi: 10.1021/jm0512847.

Abstract

Synthesis of three novel 2'-deoxy-2'-[18F]fluoro-1-beta-D-arabinofuranosyluracil derivatives [18F]FPAU, [18F]FBrVAU, and [18F]FTMAU is reported. The compounds were synthesized by coupling of 1-bromo-2-deoxy-2-fluoro sugars with corresponding silylated uracil derivatives. In vitro cell uptake indicated that all three compounds are taken up selectively in RG2TK+ cells with negligible uptake in RG2 cells. The results indicate that [18F]FBrVAU and [18F]FTMAU have better uptake profiles in comparison to [18F]FPAU and have potential as PET probes for imaging HSV1-tk gene expression.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Drug Evaluation, Preclinical
  • Fluorine Radioisotopes
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Herpesvirus 1, Human / drug effects
  • Herpesvirus 1, Human / enzymology*
  • In Vitro Techniques
  • Molecular Structure
  • Positron-Emission Tomography / methods*
  • Pyrimidine Nucleosides / chemical synthesis*
  • Pyrimidine Nucleosides / chemistry
  • Pyrimidine Nucleosides / pharmacokinetics*
  • Rats
  • Stereoisomerism
  • Thymidine Kinase / drug effects
  • Thymidine Kinase / genetics*
  • Time Factors

Substances

  • Fluorine Radioisotopes
  • Pyrimidine Nucleosides
  • Thymidine Kinase