Radiosynthesis and pre-clinical evaluation of [18F]fluoro-[1,2-2H4]choline

Graham Smith, Yongjun Zhao, Julius Leyton, Bo Shan, Quang de Nguyen, Meg Perumal, David Turton, Erik Årstad, Sajinder K. Luthra, Edward G. Robins, Eric O. Aboagye

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Introduction: Choline radiotracers are widely used for clinical PET diagnosis in oncology. [11C]Choline finds particular utility in the imaging of brain and prostate tumor metabolic status, where 2-[18F]fluoro-2-deoxy-d-glucose ('FDG') shows high background uptake. More recently we have extended the clinical utility of [11C]choline to breast cancer where radiotracer uptake correlates with tumor aggressiveness (grade). In the present study, a new choline analog, [18F]fluoro-[1,2-2H4]choline, was synthesized and evaluated as a potential PET imaging probe. Methods: [18F]Fluorocholine, [18F]fluoro-[1-2H2]choline and [18F]fluoro-[1,2-2H4]choline were synthesized by alkylation of the relevant precursor with [18F]fluorobromomethane or [18F]fluoromethyl tosylate. Radiosynthesis of [18F]fluoromethyl tosylate required extensive modification of the existing method. [18F]Fluorocholine and [18F]fluoro-[1,2-2H4]choline were then subjected to in vitro oxidative stability analysis in a chemical oxidation model using potassium permanganate and an enzymatic model using choline oxidase. The two radiotracers, together with the corresponding di-deuterated compound, [18F]fluoro-[1-2H2]choline, were then evaluated in vivo in a time-course biodistribution study in HCT-116 tumor-bearing mice. Results: Alkylation with [18F]fluoromethyl tosylate proved to be the most reliable radiosynthetic route. Stability models indicate that [18F]fluoro-[1,2-2H4]choline possesses increased chemical and enzymatic (choline oxidase) oxidative stability relative to [18F]fluorocholine. The distribution of the three radiotracers, [18F]fluorocholine, [18F]fluoro-[1-2H2]choline and [18F]fluoro-[1,2-2H4]choline, showed a similar uptake profile in most organs. Crucially, tumor uptake of [18F]fluoro-[1,2-2H4]choline was significantly increased at late time points compared to [18F]fluorocholine and [18F]fluoro-[1-2H2]choline. Conclusions: Stability analysis and biodistribution suggest that [18F]fluoro-[1,2-2H4]choline warrants further in vivo investigation as a PET probe of choline metabolism.

Original languageEnglish
Pages (from-to)39-51
Number of pages13
JournalNuclear Medicine and Biology
Issue number1
Publication statusPublished or Issued - Jan 2011
Externally publishedYes


  • Choline
  • Choline kinase
  • Fluorine-18
  • Fluorocholine
  • Isotope effect
  • Quantum tunneling

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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