Abstract
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/m2 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.
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Acknowledgments
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.
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The authors declare no conflict of interest.
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Zinn, K.R., Korb, M., Samuel, S. et al. IND-Directed Safety and Biodistribution Study of Intravenously Injected Cetuximab-IRDye800 in Cynomolgus Macaques. Mol Imaging Biol 17, 49–57 (2015). https://doi.org/10.1007/s11307-014-0773-9
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DOI: https://doi.org/10.1007/s11307-014-0773-9