Synthesis of 2'-deoxy-2'-[18F]fluoro-5-bromo-1-beta-D-arabinofuranosyluracil ([18F]-FBAU) and 2'-deoxy-2'-[18F]fluoro-5-chloro-1-beta-D-arabinofuranosyl-uracil ([18F]-FCAU), and their biological evaluation as markers for gene expression

Nucl Med Biol. 2004 May;31(4):399-405. doi: 10.1016/j.nucmedbio.2003.12.008.

Abstract

[(18)F]-FBAU and [(18)F]-FCAU have been synthesized and evaluated in vivo as markers for HSV1-tk gene expression. At 2 hours, uptake of [(18)F]-FBAU and [(18)F]-FCAU in HSV1-tk-positive tumors was 7.9-fold and 6.0-fold higher than the control tumors, respectively. Micro-PET images also showed very high uptake in HSV-tk tumors. Compared to [(14)C]-FMAU, total uptake of [(18)F]-FBAU and [(18)F]-FCAU was similar in tk-positive cells, but the uptake ratio (tk+/wild) was higher. [(18)F]-FBAU and [(18)F]-FCAU appear to be potential PET imaging agents for gene expression.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, U.S. Gov't, P.H.S.
  • Validation Study

MeSH terms

  • Animals
  • Arabinofuranosyluracil / analogs & derivatives
  • Arabinofuranosyluracil / chemistry
  • Arabinofuranosyluracil / pharmacokinetics*
  • Biomarkers, Tumor / metabolism*
  • Bromouracil / analogs & derivatives
  • Bromouracil / pharmacokinetics*
  • Colonic Neoplasms / diagnostic imaging*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Fluorouracil / analogs & derivatives
  • Fluorouracil / chemistry
  • Fluorouracil / pharmacokinetics*
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Genetic Markers / genetics
  • Humans
  • Isotope Labeling / methods
  • Metabolic Clearance Rate
  • Mice
  • Mice, Nude
  • Organ Specificity
  • Radioisotope Dilution Technique
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Thymidine Kinase / metabolism*
  • Tissue Distribution
  • Tomography, Emission-Computed / methods
  • Viral Proteins / metabolism*

Substances

  • 1-(2-fluoro-2-deoxyarabinofuranosyl)-5-bromouracil
  • 2'-deoxy-2'-fluoro-5-chloro-1-arabinofuranosyluracil
  • Biomarkers, Tumor
  • Genetic Markers
  • Radiopharmaceuticals
  • Viral Proteins
  • Arabinofuranosyluracil
  • Bromouracil
  • thymidine kinase, Canid herpesvirus 1
  • Thymidine Kinase
  • Fluorouracil