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

Abstract

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