DNA Breakage by Decay of Auger Electron Emitters: Experiments with123I-iodoHoechst 33258 and Plasmid DNA

Abstract

The Auger electron-emitting isotope 123I is of interest in the context of potential exploitation of Auger electron emitters in radioimmunotherapy. The efficiency of induction of cytotoxic lesions by decay of DNA-associated 125I, the prototype Auger electron emitter, is well established, but its long half-life (60 days) is a limitation. However, the advantage of the much shorter half-life of 123I (13.2 h) might be outweighed by its "weaker" Auger electron cascade with an average of 8-11 Auger electrons, compared to about 15-21 electrons for 125I. Accordingly, the efficiency of DNA breakage for DNA-associated 123I was investigated by incubation of 123I-iodoHoechst 33258 with plasmid DNA. The efficiency of double-strand break induction by decay of 123I was 0.62 compared to 0.82 per decay of 125I in the same experimental system. In the presence of dimethylsulfoxide, the values were 0.54 and 0.65 for decay of 123I and 125I, respectively. The results also showed that at a very low ligand/plasmid molar ratio (<1), the majority of cleavage seemed to occur at a particular site on the plasmid molecule, indicating preferential binding of the 123I-ligand to a unique site or a cluster of neighboring sites.