Molecular Imaging and Biology

, Volume 17, Issue 1, pp 49–57 | Cite as

IND-Directed Safety and Biodistribution Study of Intravenously Injected Cetuximab-IRDye800 in Cynomolgus Macaques

  • Kurt R. ZinnEmail author
  • Melissa Korb
  • Sharon Samuel
  • Jason M. Warram
  • David Dion
  • Cheryl Killingsworth
  • Jinda Fan
  • Trenton Schoeb
  • Theresa V. Strong
  • Eben L. Rosenthal
Research Article



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.


To this end, the in vivo toxicity and pharmacokinetics of IRDye800 conjugated to cetuximab (cetuximab-IRDye800; 21 mg/kg; equivalent to 250 mg/m2 human dose) were assessed in male cynomolgus monkeys over 15 days following intravenous injection and compared with an unlabeled cetuximab-dosed control group.


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.


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.

Key words

Cetuximab IRDye800 Toxicity Macaques Pharmacokinetics 



This work was supported by the UAB Small Animal Imaging Shared Facility NIH Research Core Grant (P30CA013148); NIH grants R21CA179171, T32CA091078; and an equipment loan from Novadaq and LI-COR Biosciences. The authors would like to thank Dr. Anna Sorace and Ms. Esther de Boer for assistance in this study.

Conflict of Interest

The authors declare no conflict of interest.


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Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2014

Authors and Affiliations

  • Kurt R. Zinn
    • 1
    Email author
  • Melissa Korb
    • 2
  • Sharon Samuel
    • 1
  • Jason M. Warram
    • 2
  • David Dion
    • 3
  • Cheryl Killingsworth
    • 5
  • Jinda Fan
    • 1
  • Trenton Schoeb
    • 4
  • Theresa V. Strong
    • 3
  • Eben L. Rosenthal
    • 2
  1. 1.Department of RadiologyUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Department of SurgeryUniversity of Alabama at BirminghamBirminghamUSA
  3. 3.Department of MedicineUniversity of Alabama at BirminghamBirminghamUSA
  4. 4.Department of GeneticsUniversity of Alabama at BirminghamBirminghamUSA
  5. 5.Animal Resources ProgramUniversity of Alabama at BirminghamBirminghamUSA

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