18F-labelling of oligonucleotides using succinimido 4-[18F]fluorobenzoate

A general method for the labelling of oligodeoxynucleotides and oligonucleoside phosphorothioates in the 5'-position with the positron-emitting radionuclide F-18 (t(1/2) = 110 min) is described. The label was incorporated by the reaction of succinimido 4-[F-18]fluorobenzoate 4 with oligonucleotides (18- and 20-mers) modified in the 5'-position with a hexylamine linker. Oligodeoxynucleotides 5'-GCT,AAG,CGA,TGC,CTC,CGT-3' (MTCa) and 5'-GAA,CCT,CTG,AGA,GTT,CAT,CT-3' (CROa) were labelled in 20 +/- 3% (MTCa) and 13 +/- 3% (CROa) radiochemical yields (non-isolated, decay-corrected and based on 4). Oligonucleoside phosphorothioates MTCa (S-MTCa) and CROa (S-CROa) were labelled in 9 and 7% isolated radiochemical yield, respectively (decay-corrected and based on 4). Labelled oligonucleotides and phosphorothioate analogues were separated from their unlabelled counterparts using reversed phase perfusion chromatography. The molecular mass of a labelled oligonucleotide CROa was determined by ESI-MS after a mixed F-18/F-19 fluorobenzoate labelling experiment and corresponded with the expected structure.