Fluorine-18 labeling of oligonucleotides bearing chemically-modified ribose-phosphate backbones

We have recently described the labeling of a natural deoxyribose phosphodie ster oligonucleotide with fluorine-18 (t(1/2): 109.8 min) and demonstrated its potential for in vivo imaging in a primate PET study. We here report th at the methodology employed can be reliably and routinely applied to the mo st popular chemical modifications : (a) full length internucleosidic phosph orothioate diester bonds deoxyribose oligonucleotides (the modification mos t favoured by industry for human antisense therapy), (b) hybrid methylphosp honate/phosphodiester internucleosidic bonds deoxyribose oligonucleotides a nd (c) 2'O-Methyl modified ribose oligonucleotides. The whole fluorine-18 l abeling procedure allows us to obtain 15 to 21 mCi (0.55 to 0.74 GBq) of pu re labeled oligonucleotides (regardless the modification of the sugar phosp hate backbone) in 180 minutes with a specific radioactivity of 0.8 to 2 Ci/ mu mol (30 to 70 GBq/mu mol) at the end of synthesis.