General method to label antisense oligonucleotides with radioactive halogens for pharmacological and imaging studies

Evaluation of oligonucleotides for biomedical applications requires differe nt in vivo and in vitro approaches (pharmacokinetics, biodistribution, macr o- and microimaging, metabolism,...), that are performed with different rad ioisotopes according to the temporal and spatial resolution needed. A metho d to introduce radioactive isotopes of halogens (fluorine, bromine, and iod ine) in a small and stable molecule has been developed. Radiosynthons can t hen be conjugated with any given oligonucleotide in one step to create the appropriate radiotracer. This general radiolabeling procedure for oligonucl eotides is efficient to synthesize F-18-, Br-76-, and I-125-oligonucleotide s for biological needs. Applications of the method to biodistribution, meta bolism, in vivo and ex vivo imaging of I-125- and F-18-labeled oligonucleot ides are reported.