Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques

Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging
E de BoerKurt R Zinn

Abstract

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.

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Citations

Sep 10, 2018·Journal of Surgical Oncology·Chengyue LiKenneth M Tichauer
Oct 21, 2020·Oncogene·Nicholas J EustaceChristopher D Willey
Jan 12, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Matthijs D LinssenWouter B Nagengast
Feb 16, 2019·Bioconjugate Chemistry·Jordon Sandland, Ross W Boyle

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