title: Single-dose intravenous toxicity study of IRDye 800CW in Sprague-Dawley rats.
abstract: OBJECTIVE
  Fluorophore-labeled contrast imaging agents are moving toward clinical use for a number of applications. The near-infrared dye IRDye 800CW is frequently used in its N-hydroxysuccinamide (NHS) ester form for labeling these agents. Following conjugation or breakdown of a labeled ligand, excess NHS ester is converted to the carboxylate form. To prepare for clinical use as a near-infrared fluorophore, a toxicity study was conducted on IRDye 800CW carboxylate.
  
  
  METHODS
  Male and female Sprague-Dawley rats were given a single intravenous or intradermal administration of IRDye 800CW carboxylate; Indocyanine Green was used as a comparative control. Animals were injected with varying doses of the test and control articles and observed for up to 14 days. Clinical chemistry, hematological, and pharmacokinetic analyses were performed on subgroups of animals. Organs were analyzed for content of the test article. Tissues were analyzed microscopically for pathological changes.
  
  
  RESULTS
  Based on hematologic, clinical chemistry, and histopathologic evaluation, single administration of IRDye 800CW carboxylate intravenously at dose levels of 1, 5, and 20 mg/kg or 20 mg/kg intradermally produced no pathological evidence of toxicity.
  
  
  CONCLUSIONS
  A dose of 20 mg/kg was identified as the no observed adverse effect level following IV or ID routes of administration of IRDye 800CW.
authors.affiliation: Baylor College of Medicine, Houston, TX, USA.
authors.forename: Milton V
authors.initials: MV
authors.lastname: Marshall
authors.forename: Daniel
authors.initials: D
authors.lastname: Draney
authors.forename: Eva M
authors.initials: EM
authors.lastname: Sevick-Muraca
authors.forename: D Michael
authors.initials: DM
authors.lastname: Olive
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D006403:Hematologic Tests; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D014018:Tissue Distribution
chemical_list: D005456:Fluorescent Dyes; C427728:IRDye800; D007211:Indoles