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 triplexand 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.