Vn. Karamychev et al., Distribution of DNA strand breaks produced by iodine-123 and indium-111 insynthetic oligodeoxynucleotides, ACTA ONCOL, 39(6), 2000, pp. 687-692
Antigene radiotherapy, a procedure based on delivery of short-range Auger-e
lectron-emitting radioisotopes to target genes via sequence-specific triple
r-forming oligonucleotides, has been successfully demonstrated in vitro usi
ng the well-studied radionuclide I-125. To proceed with in vivo trials, Aug
er electron emitters with shorter half-lives than I-125 are required. Here
we report a study of the efficiency and distribution of sequence-specific D
NA strand breaks produced by decay of I-123 and In-111. I-123 and In-111 we
re introduced into triplex- and duplex-forming oligodeoxyribonucleotides (O
DNs) through carbohydrate linkers of various lengths. Labeling with radioio
dine was performed through tributylstannylbenzamide intermediates while In-
111 was attached via DTPA. The Auger-emitter-labeled ODNs were hybridized t
o a single-stranded DNA target, to form duplexes. After decay accumulation,
the target DNA samples were assayed for strand breaks using a sequencing g
el-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 lo
cated 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 effectiv
ely than decay of I-123. Both I-123 and In-111 are less effective in breaki
ng DNA strands than I-125, which reflects the higher total energy of the Au
ger decay process of I-125.