title: 125I-labeled quercetin as a novel DNA-targeted radiotracer.
abstract: Quercetin is a major flavonoid that is found in most plants; it can intercalate with DNA. The purpose of this study was to investigate radiolabeling of qurecetin with (125)I, DNA binding and cellular process. In this work, quercetin was labeled with Auger emitting nuclide (125)I using chloramine-T. DNA binding of (125)I-quercetin ((125)I-Q) was investigated using cell-free in vitro assay with naked human genomic DNA in agarose plugs. Cellular uptake and nuclei accumulation were evaluated in human prostate cancer cell lines (DU 145). The internalization of (125)I-Q was evaluated with fluorescence microscopy. Cellular damage was monitored by using apoptosis assay. Quercetin was successfully labeled with (125)I, and it was taken up rapidly with cells and accumulated in the cellular nuclei. (125)I-Q-DNA binding was tight with long retention time, and it potentially induced DNA damage. These findings provide for using of (125)I-labeled quercetin as a carrier of Auger electron emitting radionuclide to the cell nuclei for targeted radiotherapy.
authors.affiliation: Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, 17 Kilometers Khazar abad Boulevard, Sari, Iran. sjhosseinim@yahoo.com
authors.forename: Seyed Jalal
authors.initials: SJ
authors.lastname: Hosseinimehr
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
authors.forename: Bo
authors.initials: B
authors.lastname: Stenerlöw
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004273:DNA, Neoplasm / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008856:Microscopy, Fluorescence; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011794:Quercetin / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D004273:DNA, Neoplasm; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011794:Quercetin