Pre-clinical study of IRDye800CW-nimotuzumab formulation, stability, pharmacokinetics, and safety

BMC Cancer

Angel Casaco¹  Darien Toledo¹  Raja Solomon Viswas²  Humphrey Fonge³  Wendy Bernhard⁴  Carolina Gonzalez⁴  Ayman El-Sayed⁴  Kris Barreto⁴  Clarence Ronald Geyer⁴  John DeCoteau⁴ 

[1] Center of Molecular Immunology, Havana, Cuba;Department of Medical Imaging, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada;Department of Medical Imaging, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada;Department of Medical Imaging, Royal University Hospital, Saskatoon, SK, Canada;Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada;

关键词: Nimotuzumab;    EGFR;    Near-infrared fluorescence imaging;    IRDye800CW;    Image-guided surgery;    Investigator’s brochure;   

DOI  :  10.1186/s12885-021-08003-3

来源: Springer

【 摘 要 】

BackgroundEpidermal growth factor receptor (EGFR) is a target for cancer therapy as it is overexpressed in a wide variety of cancers. Therapeutic antibodies that bind EGFR are being evaluated in clinical trials as imaging agents for positron emission tomography and image-guided surgery. However, some of these antibodies have safety concerns such as infusion reactions, limiting their use in imaging applications. Nimotuzumab is a therapeutic monoclonal antibody that is specific for EGFR and has been used as a therapy in a number of countries.MethodsFormulation of IRDye800CW-nimotuzumab for a clinical trial application was prepared. The physical, chemical, and pharmaceutical properties were tested to develop the specifications to determine stability of the product. The acute and delayed toxicities were tested and IRDye800CW-nimotuzumab was determined to be non-toxic. Non-compartmental pharmacokinetics analysis was used to determine the half-life of IRDye800CW-nimotuzumab.ResultsIRDye800CW-nimotuzumab was determined to be non-toxic from the acute and delayed toxicity study. The half-life of IRDye800CW-nimotuzumab was determined to be 38 ± 1.5 h. A bi-exponential analysis was also used which gave a t1/2 alpha of 1.5 h and t1/2 beta of 40.8 h.ConclusionsHere, we show preclinical studies demonstrating that nimotuzumab conjugated to IRDye800CW is safe and does not exhibit toxicities commonly associated with EGFR targeting antibodies.

【 授权许可】

CC BY