High radiochemical yield synthesis of 3'-deoxy-3'-[18F]fluorothymidine using (5'-O-dimethoxytrityl-2'-deoxy-3'-O-nosyl-beta-D-threo pentofuranosyl)thymine and its 3-N-BOC-protected analogue as a labeling precursor

Nucl Med Biol. 2003 Feb;30(2):151-7. doi: 10.1016/s0969-8051(02)00409-2.

Abstract

We prepared 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) from 3'-O-nosyl thymidine derivative 3 or its pyrimidine ring N-BOC-protected analogue 5 and optimized [(18)F]fluorination condition for a high radiochemical yield. The optimal condition for [(18)F]fluorination with precursor 3 was 30 mg (41.1 micromol)/300 microl CH(3)CN at 130 degrees C for 5 min, while precursor 5 required 34 mg (40 micromol)/300 microl CH(3)CN at 110 degrees C for 5 min. After HPLC purification at neutral pH, we achieved high radiochemical yields of 40 +/- 5.2% and 42 +/- 5.4% (decay-corrected) within 60 min of preparation time with radiochemical purities of >97%.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dideoxynucleosides / chemical synthesis*
  • Dideoxynucleosides / isolation & purification*
  • Drug Stability
  • Formic Acid Esters / chemistry
  • Isotope Labeling / methods*
  • Quality Control
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / isolation & purification
  • Thymidine / analogs & derivatives*
  • Thymidine / chemistry*

Substances

  • Dideoxynucleosides
  • Formic Acid Esters
  • Radiopharmaceuticals
  • t-butyloxycarbonyl group
  • 1-(2'-deoxy-beta-threopentofuranosyl)thymine
  • alovudine
  • Thymidine