Synthesis of [18F]-labeled (6-fluorohexyl)triphenylphosphonium cation as a potential agent for myocardial imaging using positron emission tomography

Bioconjug Chem. 2012 Mar 21;23(3):431-7. doi: 10.1021/bc2004439. Epub 2012 Feb 9.


Lipophilic cations such as phosphonium salts penetrate the hydrophobic barriers of the plasma and mitochondrial membranes and accumulate in mitochondria in response to the negative inner-transmembrane potentials. Thus, as newly developed noninvasive imaging agents, [(18)F]-labeled phosphonium salts may serve as molecular "voltage sensor" probes to investigate the role of mitochondria, particularly in myocardial disease. The present study reports the radiosynthesis of (6-fluorohexyl)triphenylphosphonium salt (3) as a potential agent for myocardial imaging by using positron emission tomography (PET). The reference compound of (6-[(18)F]fluorohexyl)triphenylphosphonium salt ([(18)F]3) was synthesized with 74% yield via three-step nucleophilic substitution reactions. The reference compound was radiolabeled via two-step nucleophilic substitution reactions of no-carrier-added [(18)F]fluoride with the precursor hexane-1,6-diyl bis(4-methylbenzenesulfonate) in the presence of Kryptofix 2.2.2 and K(2)CO(3). The radiolabeled compound was synthesized with 15-20% yield. The radiochemical purity was >98% by analytical HPLC, and the specific activity was >6.10-6.47 TBq/μmol. The cellular uptake assay showed preferential uptake of [(18)F]3 in cardiomyocytes. The results of biodistribution and micro-PET imaging studies of [(18)F]3 in mice and rats showed preferential accumulation in the myocardium. The results suggest that this compound would be a promising candidate for myocardial imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Fluorine Radioisotopes*
  • Heart / anatomy & histology*
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Inbred BALB C
  • Phosphines*
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals*
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrometry, Mass, Fast Atom Bombardment


  • (6-fluorohexyl)triphenylphosphonium
  • Fluorine Radioisotopes
  • Phosphines
  • Radiopharmaceuticals