Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques

Area of Science:

• Preclinical research
• Pharmacokinetics
• Oncology therapeutics

Background:

• Receptor-targeted antibodies conjugated to photosensitizers are promising for enhanced cancer treatment.
• Cetuximab, an EGFR antibody, is used in cancer therapy.
• IRDye700DX (IR700) is a photosensitizer for photodynamic therapy.

Purpose of the Study:

• To evaluate the biodistribution of cetuximab conjugated to IRDye700DX (cetuximab-IR700) in cynomolgus macaques.
• To facilitate clinical testing of cetuximab-IR700 for cancer treatment.

Main Methods:

• Intravenous injection of cetuximab-IR700 (40 and 80 mg/kg) into cynomolgus macaques.
• Measurement of total IR700 and intact cetuximab-IR700 in 51 tissues at 2 and 14 days post-injection.
• Comparison with a control group receiving unlabeled cetuximab.

Main Results:

• IR700 levels in tissues decreased from 34.9% at 2 days to 2.53% at 14 days post-dose.
• Highest intact cetuximab-IR700 concentrations were found in blood, lung, and skin at 2 days.
• Highest IR700 signals in tissue sections were observed in the axillary lymph node, mammary gland, and gall bladder at 2 days.

Conclusions:

• Biodistribution of IR700 and cetuximab-IR700 aligns with known epidermal growth factor receptor (EGFR) expression patterns.
• Observed changes in drug levels between 2 and 14 days indicate rapid metabolism and excretion of cetuximab-IR700.