An aminoacridine derivative for radionuclide therapy: DNA-binding properties studied in a novel cell-free in vitro assay

Erika Bohl Kullberg, Bo Stenerlöw, Senait Ghirmai, Hans Lundqvist, Per Uno Malmström, Anna Orlova, Vladimir Tolmachev, Lars Gedda

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Radiolabeled DNA-binding compounds can be used to increase the efficiency of radionuclide cancer therapy of disseminated disease. In this work, the aminoacridine compound N-[3-(acridine-9-ylamino)-propyl]-3-iodobenzamide (A3) labelled with the Auger-emitting nuclide 125I using Chloramine-T was studied. Optimal labelling conditions of 12T-A3 were investigated and the interaction with DNA was studied using a novel cell-free in vitro assay with naked human genomic DNA in agarose plugs. This novel assay showed to be simple and reliable. The results verify that 125I-A3 specifically binds DNA with low dissociation and is potent in causing double-strand breaks, yielding 1.0-1.4 breaks per decay. In conclusion, 125I-A3 is a most suitable DNA-binding compound for future therapeutic studies of Auger-electron emitters like 125I.

Original languageEnglish
Pages (from-to)1355-1360
Number of pages6
JournalInternational Journal of Oncology
Volume27
Issue number5
DOIs
Publication statusPublished - Nov 2005
Externally publishedYes

Keywords

  • Auger electron
  • DNA intercalation
  • Double-strand break
  • PFGE
  • Tumour targeting

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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