Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques
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The use of receptor-targeted antibodies conjugated to photosensitizers is actively being explored to enhance treatment efficacy. To facilitate clinical testing, we evaluated cetuximab conjugated to IRDye700DX (IR700) in cynomolgus macaques.
Total IR700 and intact cetuximab-IR700 were measured in 51 tissues at 2 and 14 days after intravenous injection of 40 and 80 mg/kg cetuximab-IR700, respectively, and compared with an unlabeled cetuximab-dosed control group (two each per sex per time point per group).
The IR700 retrieved from all tissues at 2 and 14 days after dosing was estimated at 34.9 ± 1.8 and 2.53 ± 0.67 % of the total dose, respectively. The tissues with the highest levels of intact cetuximab-IR700 at 2 days after dosing were the blood, lung, and skin. Formalin-fixed paraffin-embedded tissue sections at 2 days after dosing showed the highest IR700 signals in the axillary lymph node, mammary gland, and gall bladder.
Both IR700 and intact cetuximab-IR700 biodistributions were consistent with known epidermal growth factor receptor (EGFR) expression, and changes between 2 and 14 days were consistent with rapid metabolism and excretion of the cetuximab-IR700.
Key wordsPhotoimmunotherapy Biodistribution Macaques Cetuximab IRDye700DX
This work was supported by Aspyrian Therapeutics LLC, the UAB Comprehensive Cancer Center small animal imaging shared facility (5P30CA013148), and an equipment loan from LI-COR Biosciences. Authors would like to thank Miguel Garcia-Guzman for his input in this study.
Compliance with Ethical Standards
Conflict of Interest
Dr. K. R. Zinn reports grants from Aspyrian Therapeutics, during the conduct of the study.
All applicable institutional and/or national guidelines for the care and use of animals were followed.