One-pot multi-tracer synthesis of novel (18)F-labeled PET imaging agents

Mol Pharm. 2014 Nov 3;11(11):3818-22. doi: 10.1021/mp500324n. Epub 2014 Sep 5.

Abstract

(18)F labeled phosphonium salts are increasingly important molecular probes for targeting the mitochondrial membrane potential depletion during apoptosis and for detecting myocardial perfusion deficit. Here, we introduce three new tracers, [(18)F]MitoPhos_04, [(18)F]MitoPhos_05, and [(18)F]MitoPhos_07, that have the potential to act as mitochondrial imaging agents. Moreover, they have the added advantage of being synthesized in the same reaction vial from one radiolabeled synthon, demonstrating a new approach to synthesizing multiple tracers in one-pot, which is a highly useful means for increasing the throughput of radiotracer development. The radiosynthesis of the tracers was carried out on a fully automated system via a facile two-step reaction. Utilizing the radiolabeling of an ethyl azide, a copper-mediated 1,3-cycloaddition reaction and isolation via semiprep high-performance liquid chromatography (HPLC) allowed for the simultaneous synthesis of two or three tracers with a total synthesis time of less than 1 h.

Keywords: click chemistry; fluorine-18; mitochondria imaging; phosphonium cations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Automation
  • Azides / chemistry
  • Cations / chemistry
  • Chromatography, High Pressure Liquid
  • Click Chemistry
  • Copper / chemistry
  • Fluorine Radioisotopes / chemistry*
  • Humans
  • Isotope Labeling
  • Membrane Potential, Mitochondrial
  • Mitochondria / metabolism
  • Myocardium / pathology
  • Phosphates / chemistry*
  • Positron-Emission Tomography*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry*
  • Salts / chemistry

Substances

  • Azides
  • Cations
  • Fluorine Radioisotopes
  • Phosphates
  • Radiopharmaceuticals
  • Salts
  • Copper