Strand breakage by decay of DNA-bound 124I provides a basis for combined PET imaging and Auger endoradiotherapy

Pavel Lobachevsky, George R. Clark, Patrycja D. Pytel, Brenda Leung, Colin Skene, Laura Andrau, Jonathan M. White, Tom Karagiannis, Carleen Cullinane, Boon Q. Lee, Andrew Stuchbery, Tibor Kibedi, Rodney J. Hicks, Roger F. Martin

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4 Citations (Scopus)


Purpose: DNA ligands labelled with 125I induce cytotoxic DNA double-strand breaks (DSB), suggesting a potential for Auger endoradiotherapy. Since the 60-day half-life of 125I is suboptimal for therapy, we have investigated another Auger-emitter 124I, with shorter half-life (4.18 days), and the additional feature of positron-emission, enabling positron emission tomography (PET) imaging. The purpose of this study was to compare the two radionuclides on the basis of DNA DSB per decay. Materials and methods: Using a 124I- (or 125I)-labelled minor groove binding DNA ligand, we investigated DNA breakage using the plasmid DNA assay. Biodistribution of the conjugate of the labelled ligand with transferrin was investigated in nude mice bearing a K562 human lymphoma xenograft. Results: The probability of DSB per decay was 0.58 and 0.85 for 124I and 125I, respectively, confirming the therapeutic potential of the former. The crystal structure of the ligand DNA complex shows the iodine atom deep within the minor groove, consistent with the high efficiency of induced damage. Biodistribution studies, including PET imaging, showed distinctive results for the conjugate, compared to the free ligand and transferrin, consistent with receptor-mediated delivery of the ligand. Conclusions: Conjugation of 124I-labelled DNA ligands to tumor targeting peptides provides a feasible strategy for Auger endoradiotherapy, with the advantage of monitoring tumor targeting by PET imaging.

Original languageEnglish
Pages (from-to)686-697
Number of pages12
JournalInternational Journal of Radiation Biology
Issue number11
Publication statusPublished - Nov 2016
Externally publishedYes


  • Auger electrons
  • Auger emitters
  • Auger endoradiotherapy
  • DNA double-strand breaks
  • iodine-124
  • Monte Carlo simulation

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