Distribution of DNA strand breaks produced by iodine-123 and indium-111 in synthetic oligodeoxynucleotides

Antigene radiotherapy, a procedure based on delivery of short-range Auger-electron-emitting radioisotopes to target genes via sequence-specific tripler-forming oligonucleotides, has been successfully demonstrated in vitro using the well-studied radionuclide I-125. To proceed with in vivo trials, Auger electron emitters with shorter half-lives than I-125 are required. Here we report a study of the efficiency and distribution of sequence-specific DNA strand breaks produced by decay of I-123 and In-111. I-123 and In-111 were introduced into triplex- and duplex-forming oligodeoxyribonucleotides (ODNs) through carbohydrate linkers of various lengths. Labeling with radioiodine was performed through tributylstannylbenzamide intermediates while In-111 was attached via DTPA. The Auger-emitter-labeled ODNs were hybridized to a single-stranded DNA target, to form duplexes. After decay accumulation, the target DNA samples were assayed for strand breaks using a sequencing gel-electrophoresis technique. For the first time, we observed footprints of DNA strand breaks produced by I-123 and In-111. Most of the breaks were located within 10 nucleotides from the decay site. The yield of strand breaks per decay varies; decay of In-111 breaks DNA almost 10 times more effectively than decay of I-123. Both I-123 and In-111 are less effective in breaking DNA strands than I-125, which reflects the higher total energy of the Auger decay process of I-125.