3,4,5-Tri-
O-acet
yl-2-[
18F]fluoro-2-deox
y-
D-glucop
yranos
yl 1-phen
ylthiosulfonate (Ac
3-[
18F]FGlc-PTS) was developed as a thiol-reactive labeling reagent for the site-specific
18F-gl
ycos
ylation of peptides. Taking advantageof highl
y accessible 1,3,4,6-tetra-
O-acet
yl-2-deox
y-2-[
18F]fluoroglucop
yranose, a three-step radiochemical pathwa
ywas investigated and optimized, providing Ac
3-[
18F]FGlc-PTS in a radiochemical
yield of about 33% in 90 min(deca
y-corrected and based on starting [
18F]fluoride). Ac
3-[
18F]FGlc-PTS was reacted with the model pentapeptideCAKAY, confirming chemoselectivit
y and excellent conjugation
yields of >90% under mild reaction conditions.The optimized method was adopted to the
18F-gl
ycos
ylation of the
v
3-affine peptide c(RGDfC), achieving highconjugation
yields (95%, deca
y-corrected). The
v
3 binding affinit
y of the gl
ycos
ylated c(RGDfC) remaineduninfluenced as determined b
y competition binding studies versus
125I-echistatin using both isolated
v
3 andhuman umbilical vein endothelial cells (
Ki = 68 ± 10 nM (
v
3) versus
Ki = 77 ± 4 nM (HUVEC)). The wholeradios
ynthetic procedure, including the preparation of the
18F-gl
ycos
ylating reagent Ac
3-[
18F]FGlc-PTS, peptideligation, and final HPLC purification, provided a deca
y-uncorrected radiochemical
yield of 13% after a totals
ynthesis time of 130 min. Ac
3-[
18F]FGlc-PTS represents a novel
18F-labeling reagent for the mild chemoselective
18F-gl
ycos
ylation of peptides indicating its potential for the design and development of
18F-labeled bioactiveS-gl
ycopeptides suitable to stud
y their pharmacokinetics in vivo b
y positron emission tomograph
y (PET).