IND-directed safety and biodistribution study of intravenously injected cetuximab-IRDye800 in cynomolgus macaques

Mol Imaging Biol. 2015 Feb;17(1):49-57. doi: 10.1007/s11307-014-0773-9.


Purpose: 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.

Procedures: 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal, Humanized / chemistry*
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Cetuximab
  • Dose-Response Relationship, Drug
  • Electrocardiography
  • Fluorescent Dyes / chemistry*
  • Indoles / chemistry*
  • Indoles / pharmacokinetics*
  • Injections, Intravenous
  • Macaca fascicularis
  • Male
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Neoplasms / surgery
  • Signal-To-Noise Ratio
  • Tissue Distribution


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Fluorescent Dyes
  • IRDye800
  • Indoles
  • Cetuximab