Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques.

Purpose: 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.Procedures: Total IR700 and intact cetuximab-IR700...

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Detalles Bibliográficos
Publicado en:Molecular Imaging & Biology Vol. 18; no. 2; pp. 232 - 243
Autores principales: Boer, E., Samuel, S., French, D., Warram, J., Schoeb, T., Rosenthal, E., Zinn, K., de Boer, E, French, D N, Warram, J M, Schoeb, T R, Rosenthal, E L, Zinn, K R
Formato: research Journal Article
Publicado: Springer Nature Apr2016
Acceso en línea:Ver este registro en EBSCOhost
Descripción
Sumario:Purpose: 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.Procedures: 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).Results: 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.Conclusions: 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.