TMSOTf assisted synthesis of 2'-deoxy-2'-[18F]fluoro-β-D-arabinofuranosylcytosine ([18F]FAC)

PLoS One. 2018 May 1;13(5):e0196784. doi: 10.1371/journal.pone.0196784. eCollection 2018.

Abstract

[18F]FAC (2'-deoxy-2'-[18F]fluoro-β-D-arabinofuranosylcytosine, 1) is a versatile probe for imaging deoxycytidine kinase (dCK) expression levels in vivo. dCK is responsible for phosphorylation of deoxycytidine (dC, 2) and other nucleoside analogs, plays a key role in immune activation and has demonstrated to be one of the key enzymes in activating nucleoside based drugs including gemcitabine. Reported synthesis of [18F]FAC is high yielding but is quite challenging requiring bromination using HBr and careful drying of excess HBr which is critical for successful synthesis. Here in we report a simplified trimethylsilyl trifluoromethanesulfonate (TMSOTf) assisted synthesis of [18F]FAC eliminating the need of bromination and drying. [18F]FAC (β-anomer) was synthesized with average isolated decay corrected yield of 10.59 + 4.2% (n = 6) with radiochemical purity of >98% and total synthesis time of 158 + 19 min.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytarabine / chemistry*
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / chemistry
  • Deoxycytidine Kinase / chemistry
  • Fluorine Radioisotopes / chemistry*
  • Gemcitabine
  • Mesylates / chemistry*
  • Radiochemistry / methods
  • Radiopharmaceuticals / chemistry*
  • Trimethylsilyl Compounds / chemistry*

Substances

  • Fluorine Radioisotopes
  • Mesylates
  • Radiopharmaceuticals
  • Trimethylsilyl Compounds
  • Cytarabine
  • Deoxycytidine
  • trimethylsilyl trifluoromethanesulfonate
  • Deoxycytidine Kinase
  • Fluorine-18
  • Gemcitabine