In Vivo Optical Imaging of Acute Cell Death Using a Near-Infrared Fluorescent Zinc−Dipicolylamine Probe

• Published in: Molecular pharmaceutics 2011-04, Vol.8 (2), p.583-590
• Main Authors: Smith, Bryan A, Gammon, Seth T, Xiao, Shuzhang, Wang, Wei, Chapman, Sarah, McDermott, Ryan, Suckow, Mark A, Johnson, James R, Piwnica-Worms, David, Gokel, George W, Smith, Bradley D, Leevy, W. Matthew
• Format: Article
• Language: English
• Subjects: Animals; Cell Death; Fluorescent Dyes - pharmacokinetics; Infrared Rays; Mice; Mice, Nude; Molecular Imaging; Muscle, Skeletal - pathology; Organometallic Compounds - pharmacokinetics; Picolines - pharmacokinetics; Spectroscopy, Near-Infrared; Zinc - chemistry
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/mp100395u

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.