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

Evaluation of oligonucleotides for biomedical applications requires different in vivo and in vitro approaches (pharmacokinetics, biodistribution, macro- and microimaging, metabolism, ...), that are performed with different radioisotopes according to the temporal and spatial resolution needed. A method to introduce radioactive isotopes of halogens (fluorine, bromine, and iodine) in a small and stable molecule has been developed. Radiosynthons can then be conjugated with any given oligonucleotide in one step to create the appropriate radiotracer. This general radiolabeling procedure for oligonucleotides is efficient to synthesize ¹⁸F-, ⁷⁶Br-, and ¹²⁵I-oligonucleotides for biological needs. Applications of the method to biodistribution, metabolism, in vivo and ex vivo imaging of ¹²⁵I- and ¹⁸F-labeled oligonucleotides are reported.