17-[4-(2-[18F]fluoroethyl)-1H-1,2,3-triazol-1-yl]-6-thia-heptadecanoic acid: a potential radiotracer for the evaluation of myocardial fatty acid metabolism

Bioconjug Chem. 2009 Jun;20(6):1139-45. doi: 10.1021/bc800472a.

Abstract

In this study, we synthesized 17-[4-(2-[(18)F]fluoroethyl)-1H-1,2,3-triazol-1-yl]-6-thia-heptadecanoic acid ([(18)F]1), a PET radiotracer for the evaluation of fatty acid metabolism. [(18)F]1 was synthesized in 20-26% decay-corrected radiochemical yields from 17-azido 6-thia-heptadecanoic acid (9) and 4-[(18)F]fluoro-1-butyne using click chemistry. The tissue distribution of [(18)F]1 in mice showed high radioactivity accumulation in heart (3.70%ID/g at 1 min, 3.28%ID/g at 10 min, and 3.01%ID/g at 60 min postinjection), a prolonged myocardial elimination half-life (>60 min), and a maximal heart-to-blood uptake ratio at 5 min postinjection (5.55). Pretreatment with etomoxir, a carnitine palmitoyl transferase (CPT) I inhibitor, reduced myocardial radioactivity uptake at 30 min postinjection by 53%, suggesting that [(18)F]1 was transported into the mitochondria. Analyses of heart tissue samples showed that most of the radioactivity was present in a tissue pellet (62-63%) after homogenization in CHCl(3)-CH(3)OH followed by extraction with 40% urea and 5% H(2)SO(4), which was mostly precipitated with addition of 50% trichloroacetic acid (TCA). These results suggest that [(18)F]1 undergoes metabolic trapping via beta-oxidation in myocardium and, thus, suggest that it has potential use as a PET radiotracer for the evaluation of myocardial fatty acid metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fatty Acids / chemical synthesis
  • Fatty Acids / metabolism*
  • Fatty Acids / pharmacokinetics
  • Heart / diagnostic imaging
  • Male
  • Mice
  • Mice, Inbred ICR
  • Myocardium / metabolism*
  • Positron-Emission Tomography
  • Radioactive Tracers
  • Tissue Distribution
  • Triazoles / chemical synthesis
  • Triazoles / metabolism*
  • Triazoles / pharmacokinetics

Substances

  • 17-(4-(2-fluoroethyl)-1H-1,2,3-triazol-1-yl)-6-thia-heptadecanoic Acid
  • Fatty Acids
  • Radioactive Tracers
  • Triazoles