Imaging of protein synthesis: in vitro and in vivo evaluation of (44)Sc-DOTA-puromycin

Mol Imaging Biol. 2013 Feb;15(1):79-86. doi: 10.1007/s11307-012-0561-3.

Abstract

Purpose: The purpose of this study was to investigate whether (44)Sc-labeled puromycin can be utilized for imaging of protein synthesis in vivo.

Methods: For micro-positron emission tomographic (μPET) studies, 20-25 MBq of [(44)Sc]-DOTA-puromycin was administered to tumor-bearing rats, and animals were scanned for 1 h dynamically. Results were further validated by dissecting organs and tissues of the animals after the measurement and in vitro blocking experiments using puromycin or cycloheximide to block protein synthesis.

Results: μPET images of tumor-bearing rats showed significant tumor uptake of [(44)Sc]-DOTA-puromycin and a clear-cut tumor visualization. In both blocking experiments, cellular uptake of [(44)Sc]-DOTA-puromycin ([(44)Sc]-DOTA-Pur) could be suppressed by blocking protein synthesis.

Conclusions: We report for the first time successful μPET imaging with (44)Sc obtained from a (44)Ti/(44)Sc generator, as well as noninvasive μPET imaging of ribosomal activity, respectively protein synthesis, with a puromycin-based radiopharmaceutical and the direct correlation between cellular uptake of [(44)Sc]-DOTA-Pur and protein synthesis.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics*
  • Heterocyclic Compounds, 1-Ring / pharmacology
  • Humans
  • Kinetics
  • Male
  • Molecular Imaging / methods*
  • Positron-Emission Tomography
  • Protein Biosynthesis
  • Proteins / analysis*
  • Proteins / chemistry
  • Proteins / metabolism
  • Puromycin / analogs & derivatives*
  • Puromycin / pharmacokinetics
  • Puromycin / pharmacology
  • Rats
  • Scandium / chemistry
  • Scandium / pharmacokinetics*
  • Tissue Distribution

Substances

  • Heterocyclic Compounds, 1-Ring
  • Proteins
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • Puromycin
  • Scandium