Labeling of an antisense oligonucleotide with [(18)F]FPy5yne.
Functional imaging of gene expression in vivo with short-lived positron emitter (18)F remains an unrealized goal, in part because the long reaction times and challenging protocols typically required to label nucleic acid-based molecular probes with this radionuclide (t(1/2) = 109.8 minutes). To this end, we synthesized prosthetic group 2-[(18)F]fluoro-3-(hex-5-ynyloxy)pyridine ([(18)F]FPy5yne), used previously to label peptides, and coupled it to an oligodeoxyribonucleotide with (18)F by way of a Cu(I)-mediated azide/alkyne cycloaddition reaction. HPLC-purified [(18)F]FPy5yne was ligated to a 5'-azide-modified DNA sequence antisense to mdr1 mRNA in the presence of Cu(I)-stabilizing ligand tris(benzyltriazolylmethyl)amine and 2,6-lutidine. Non-decay corrected, collected yields of the (18)F-labeled oligonucleotide from end-of-bombardment were 3.9% +/- 0.5% (n = 3; 24.6% +/- 0.5% decay corrected). Shortest preparation time was 276 minutes from start of synthesis.
Inkster
James A H
JA
Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada. jamesi@triumf.ca
Adam
Michael J
MJ
Storr
Tim
T
Ruth
Thomas J
TJ
D005462:Fluorine Radioisotopes; D007553:Isotope Labeling / Q000379:methods; D015394:Molecular Structure; D016376:Oligonucleotides, Antisense / Q000737:chemistry*
D005462:Fluorine Radioisotopes; D016376:Oligonucleotides, Antisense