title: In vivo optical imaging of acute cell death using a near-infrared fluorescent zinc-dipicolylamine probe.
abstract: Cell death is a fundamental biological process that is present in numerous disease pathologies. Fluorescent probes that detect cell death have been developed for a myriad of research applications ranging from microscopy to in vivo imaging. Here we describe a synthetic near-infrared (NIR) conjugate of zinc(II)-dipicolylamine (Zn²+-DPA) for in vivo imaging of cell death. Chemically induced in vivo models of myopathy were established using an ionphore, ethanol, or ketamine as cytotoxins. The Zn²+-DPA fluorescent probe or corresponding control was subsequently injected, and whole animal fluorescence imaging demonstrated probe uptake at the site of muscle damage, which was confirmed by ex vivo and histological analyses. Further, a comparative study with a NIR fluorescent conjugate Annexin V showed less intense uptake at the site of muscle damage and high accumulation in the bladder. The results indicate that the fluorescent Zn²+-DPA conjugate is an effective probe for in vivo cell death detection and in some cases may be an appropriate alternative to fluorescent Annexin V conjugates.
authors.affiliation: Department of Chemistry and Biochemistry, 236 Nieuwland Science Hall, University of Notre Dame, Notre Dame, Indiana 46556, USA.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Smith
authors.forename: Seth T
authors.initials: ST
authors.lastname: Gammon
authors.forename: Shuzhang
authors.initials: S
authors.lastname: Xiao
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Sarah
authors.initials: S
authors.lastname: Chapman
authors.forename: Ryan
authors.initials: R
authors.lastname: McDermott
authors.forename: Mark A
authors.initials: MA
authors.lastname: Suckow
authors.forename: James R
authors.initials: JR
authors.lastname: Johnson
authors.forename: David
authors.initials: D
authors.lastname: Piwnica-Worms
authors.forename: George W
authors.initials: GW
authors.lastname: Gokel
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Smith
authors.forename: W Matthew
authors.initials: WM
authors.lastname: Leevy
mesh_terms: D000818:Animals; D016923:Cell Death; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D007259:Infrared Rays; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging; D018482:Muscle, Skeletal / Q000473:pathology*; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D010847:Picolines / Q000493:pharmacokinetics; D019265:Spectroscopy, Near-Infrared; D015032:Zinc / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D009942:Organometallic Compounds; D010847:Picolines; C509592:zinc(II) dipicolylamine; D015032:Zinc