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An aminoacridine derivative for radionuclide therapy: DNA binding properties studied in a novel cell-free in vitro assay
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
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2005 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 27, no 5, 1355-60 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2005. Vol. 27, no 5, 1355-60 p.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-104630PubMedID: 16211232OAI: oai:DiVA.org:uu-104630DiVA: diva2:220025
Available from: 2009-05-29 Created: 2009-05-29 Last updated: 2017-12-13Bibliographically approved

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Orlova, AnnaTolmachev, Vladimir

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Biomedical Radiation SciencesDepartment of Biochemistry and Organic ChemistryDepartment of Surgical Sciences
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