An aminoacridine derivative for radionuclide therapy: DNA binding properties studied in a novel cell-free in vitro assay |
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Authors: | Kullberg Erika Bohl Stenerlöw Bo Ghirmai Senait Lundqvist Hans Malmström Per-Uno Orlova Anna Tolmachev Vladimir Gedda Lars |
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Affiliation: | Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, SE-751 85 Uppsala, Sweden. |
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Abstract: | Radiolabelled 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 125I-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. |
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