Synthesis of 3′-deoxy-3′-fluorothymidine (FLT) 5′-O-glucuronide: a reference standard for imaging studies with [18F]FLT

Abstract

Reaction of methyl 2,3,4-tri-O-acetyl-1-O-(trichloroacetimidoyl)-α-D-glucopyranuronate with 3′-deoxy-3′-fluorothymidine in the presence of trimethylsilyl trifluoromethanesulfonate gave (2R,3R,4S,5S,6S)-2-(((2R,3S,5R)-3-fluoro-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate, which was hydrolysed to 3′-deoxy-3′-fluorothymidine-5′-glucuronide. Analysis of this reference standard by high performance liquid chromatography enabled the identification of [¹⁸F]3′-deoxy-3′-fluorothymidine-5′-glucuronide in blood samples from six human patients who had been administered [¹⁸F]3′-deoxy-3′-fluorothymidine.