title: IND-directed safety and biodistribution study of intravenously injected cetuximab-IRDye800 in cynomolgus macaques.
abstract: OBJECTIVE
  The use of receptor-targeted antibodies conjugated to fluorophores is actively being explored for real-time imaging of disease states; however, the toxicity of the bioconjugate has not been assessed in non-human primates.
  
  
  METHODS
  To this end, the in vivo toxicity and pharmacokinetics of IRDye800 conjugated to cetuximab (cetuximab-IRDye800; 21 mg/kg; equivalent to 250 mg/m(2) human dose) were assessed in male cynomolgus monkeys over 15 days following intravenous injection and compared with an unlabeled cetuximab-dosed control group.
  
  
  RESULTS
  Cetuximab-IRDye800 was well tolerated. There were no infusion reactions, adverse clinical signs, mortality, weight loss, or clinical histopathology findings. The plasma half-life for the cetuximab-IRDye800 and cetuximab groups was equivalent (2.5 days). The total recovered cetuximab-IRDye800 in all tissues at study termination was estimated to be 12 % of the total dose. Both cetuximab-IRDye800 and cetuximab groups showed increased QTc after dosing. The QTc for the cetuximab-dosed group returned to baseline by day 15, while the QTc of the cetuximab-IRDye800 remained elevated compared to baseline.
  
  
  CONCLUSIONS
  IRDye800 in low molar ratios does not significantly impact cetuximab half-life or result in organ toxicity. These studies support careful cardiac monitoring (ECG) for human studies using fluorescent dyes.
authors: Department of Radiology, University of Alabama at Birmingham, Volker Hall G082, 1670 University Boulevard, Birmingham, AL, 35294, USA, kurtzinn@uab.edu.
authors: Kurt R
authors: KR
authors: Zinn
authors: Melissa
authors: M
authors: Korb
authors: Sharon
authors: S
authors: Samuel
authors: Jason M
authors: JM
authors: Warram
authors: David
authors: D
authors: Dion
authors: Cheryl
authors: C
authors: Killingsworth
authors: Jinda
authors: J
authors: Fan
authors: Trenton
authors: T
authors: Schoeb
authors: Theresa V
authors: TV
authors: Strong
authors: Eben L
authors: EL
authors: Rosenthal
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry* / Q000493:pharmacokinetics*; D000068818:Cetuximab; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005456:Fluorescent Dyes / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry* / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D059629:Signal-To-Noise Ratio; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005456:Fluorescent Dyes; C427728:IRDye800; D007211:Indoles; D000068818:Cetuximab