title: An aminoacridine derivative for radionuclide therapy: DNA binding properties studied in a novel cell-free in vitro assay.
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.
authors.affiliation: Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, SE-751 85 Uppsala, Sweden.
authors.forename: Erika Bohl
authors.initials: EB
authors.lastname: Kullberg
authors.forename: Bo
authors.initials: B
authors.lastname: Stenerlöw
authors.forename: Senait
authors.initials: S
authors.lastname: Ghirmai
authors.forename: Hans
authors.initials: H
authors.lastname: Lundqvist
authors.forename: Per-Uno
authors.initials: PU
authors.lastname: Malmström
authors.forename: Anna
authors.initials: A
authors.lastname: Orlova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
authors.forename: Lars
authors.initials: L
authors.lastname: Gedda
mesh_terms: D000166:Acridines / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D001681:Biological Assay / Q000379:methods; D002474:Cell-Free System; D002700:Chloramines; D018736:DNA Adducts; D004249:DNA Damage; D006801:Humans; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D009369:Neoplasms / Q000532:radiotherapy; D012685:Sepharose; D014105:Tosyl Compounds
chemical_list: D000166:Acridines; D001549:Benzamides; D002700:Chloramines; D018736:DNA Adducts; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; C506214:N-(3-(acridin-9-yl)propyl)-3-iodobenzamide; D014105:Tosyl Compounds; C016300:chloramine-T; D012685:Sepharose