Evaluation of [76Br]FBAU 3',5'-dibenzoate as a lipophilic prodrug for brain imaging

Nucl Med Biol. 2002 Jul;29(5):527-35. doi: 10.1016/s0969-8051(02)00324-4.

Abstract

[76Br]FBAU is a potential PET tracer for assessing proliferation. This study proposes that [76Br]FBAU 3',5'-dibenzoate has higher blood-brain-barrier permeability than [76Br]FBAU itself and thus might be better suited for applications in the brain. The brain uptake indexes of the two compounds measured after carotid injection (29.6 +/- 13.9 for [76Br]FBAU 3',5'-dibenzoate, versus 10.0 +/- 8.7 for [76Br]FBAU) support this claim. Biodistribution study also showed that the brain accumulation of activity was higher in rats injected with [76Br]FBAU 3',5'-dibenzoate than with [76Br]FBAU (0.119+/-0.023 DUR at 1 h, versus 0.061 +/- 0.006). [76Br]FBAU 3',5'-dibenzoate was relatively stable in rat plasma, gradually being hydrolyzed to [76Br]FBAU exponentially with a calculated half-life of 0.8 h. DNA incorporation of [76Br]FBAU was also confirmed. The results presented support the hypothesis that the 3',5'-dibenzoate can act as a prodrug for FBAU and deliver more radiolabeled nucleoside to the brain.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Animals
  • Brain / metabolism*
  • Bromouracil / analogs & derivatives
  • Bromouracil / chemical synthesis
  • Bromouracil / pharmacokinetics*
  • DNA / metabolism
  • Female
  • Hydrolysis
  • Male
  • Models, Chemical
  • Models, Molecular
  • Prodrugs / pharmacokinetics*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Distribution

Substances

  • 1-(2-fluoro-2-deoxy-3,5-O-dibenzoylarabinofuranosyl)-5-bromouracil
  • 1-(2-fluoro-2-deoxyarabinofuranosyl)-5-bromouracil
  • Prodrugs
  • Radiopharmaceuticals
  • Bromouracil
  • DNA