title: Development of double-stranded siRNA labeling method using positron emitter and its in vivo trafficking analyzed by positron emission tomography.
abstract: Pharmacokinetic study of small interfering RNA (siRNA) is an important issue for the development of siRNAs for use as a medicine. For this purpose, a novel and favorable positron emitter-labeled siRNA was prepared by amino group-modification using N-succinimidyl 4-[fluorine-18] fluorobenzoate ([(18)F]SFB), and real-time analysis of siRNA trafficking was performed by using positron emission tomography (PET). Naked [(18)F]-labeled siRNA or cationic liposome/[(18)F]-labeled siRNA complexes were administered to mice, and differential biodistribution of the label was imaged by PET. The former was cleared quite rapidly from the bloodstream and excreted from the kidneys; but in contrast, the latter tended to accumulate in the lungs. We also confirmed the biodistribution of fluorescence-labeled naked siRNA and cationic liposome/siRNA complexes by use of a near-infrared fluorescence imaging system. As a result, a similar biodistribution was observed, although quantitative data were obtained only by planar positron imaging system (PPIS) analysis but not by fluorescence in vivo imaging. Our results indicate that PET imaging of siRNA provides important information for the development of siRNA medicines.
authors.affiliation: Department of Medical Biochemistry and Global COE Program, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka-city, Shizuoka 422-8526, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hatanaka
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Asai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koide
authors.forename: Eriya
authors.initials: E
authors.lastname: Kenjo
authors.forename: Takuma
authors.initials: T
authors.lastname: Tsuzuku
authors.forename: Norihiro
authors.initials: N
authors.lastname: Harada
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukada
authors.forename: Naoto
authors.initials: N
authors.lastname: Oku
mesh_terms: D000818:Animals; D001565:Benzoates / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D019788:Fluorodeoxyglucose F18 / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D007553:Isotope Labeling; D008081:Liposomes / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D034741:RNA, Small Interfering / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D013388:Succinimides / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D001565:Benzoates; D008081:Liposomes; D034741:RNA, Small Interfering; D013388:Succinimides; D019788:Fluorodeoxyglucose F18; C075713:N-succinimidyl-4-fluorobenzoate