Synthesis and evaluation of (18)F-trifluoroborate derivatives of triphenylphosphonium for myocardial perfusion imaging

Bioorg Med Chem Lett. 2016 Apr 1;26(7):1675-9. doi: 10.1016/j.bmcl.2016.02.062. Epub 2016 Feb 22.

Abstract

Four trifluoroborate derivatives of phosphonium cations 2a-d were radiolabeled with fluorine-18 ((18)F) and evaluated for imaging myocardial perfusion with positron emission tomography (PET). Tracers were radiolabeled simply via (18)F-(19)F isotope exchange reaction in acidic (pH 2) aqueous solution. On average, [(18)F]2a-d were obtained in 10-17% non-decay-corrected radiochemical yield with 25.9-48.1GBq/μmol specific activity, and >96% radiochemical purity. In vitro stability study showed no decomposition of [(18)F]2a-d after being incubated in mouse plasma for up to 2h. Myocardial uptake in mice was visualized in PET images by using [(18)F]2b-d but not [(18)F]2a. [(18)F]2a-d were stable against in vivo defluorination as no significant bone uptake was observed. Despite sub-optimal heart uptake of [(18)F]2b-d, we successfully demonstrated that (18)F-(19)F isotope exchange reaction on trifluoroborates could be a promising strategy for the design of potential (18)F-labeled tracers even for intracellular targets.

Keywords: Fluorine-18; Myocardial perfusion imaging; Positron emission tomography; Thyroid; Trifluoroborate; Triphenylphosphonium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Borates / chemistry*
  • Borates / pharmacokinetics
  • Fluorine Radioisotopes / chemistry*
  • Fluorine Radioisotopes / pharmacokinetics
  • Heart / diagnostic imaging
  • Mice
  • Myocardial Perfusion Imaging / methods*
  • Myocardium / metabolism
  • Organophosphorus Compounds / chemistry*
  • Organophosphorus Compounds / pharmacokinetics
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics

Substances

  • Borates
  • Fluorine Radioisotopes
  • Organophosphorus Compounds
  • Radiopharmaceuticals