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

Abstract

We have recently described the labeling of a natural deoxyribose phosphodiester oligonucleotide with fluorine-18 (t1/2 : 109·8 min) and demonstrated its potential for in vivo imaging in a primate PET study. We here report that the methodology employed can be reliably and routinely applied to the most popular chemical modifications: (a) full length internucleosidic phosphorothioate diester bonds deoxyribose oligonucleotides (the modification most favoured by industry for human antisense therapy), (b) hybrid methylphosphonate/phosphodiester internucleosidic bonds deoxyribose oligonucleotides and (c) 2′Methyl modified ribose oligonucleotides. The whole fluorine-18 labeling procedure allows us to obtain 15 to 21 mCi (0·55 to 0·74 GBq) of pure labeled oligonucleotides (regardless the modification of the sugar phosphate backbone) in 180 minutes with a specific radioactivity of 0·8 to 2 Ci/μmol (30 to 70 GBq/μmol) at the end of synthesis. Copyright © 2000 John Wiley & Sons, Ltd.