90Y-DOTA-nimotuzumab: Synthesis of a Promising β⁻ radiopharmaceutical

2021 ◽  
Vol 13 ◽  
Author(s):  
Teresa Scotognella ◽  
Daria Maccora ◽  
Isabella Bruno ◽  
Marco Chinol ◽  
Massimo Castagnola ◽  
...  
Keyword(s):  
Human Plasma ◽  
Radiochemical Purity ◽  
Growth Factor Receptor ◽  
Reaction Volume ◽  
Physiological Conditions ◽  
Guided Surgery ◽  
New Radio ◽  
Epidermal Growth ◽  
Optimized Conditions ◽  
Fold Excess

Background: Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody, nowadays used for tumour immunochemotherapy. This study aimed to label the conjugate DOTA-nimotuzumab with yttrium-90, in order to provide a β- emitting radioimmunoconjugate (90Y-DOTA-nimotuzumab) potentially useful to assess the feasibility of a new radio-guided surgery approach. Methods: The synthesis of 90Y-DOTA-nimotuzumab was performed in two days. Nimotuzumab was conjugated with a 50 fold excess of DOTA and then labelled with 90Y3+. The 90Y-DOTA-nimotuzumab preparation was optimized considering several parameters such as pH, temperature and reaction volume. Moreover, the 90Y-DOTA-nimotuzumab stability was evaluated in human plasma. Results: The radioimmunoconjugate 90Y-DOTA-nimotuzumab was obtained with a radiochemical purity greater than 96%, and showed a good stability at 20°C as well as at 37°C in human plasma. Conclusions: The optimized conditions for a mild and easy preparation of 90Y-DOTA-nimotuzumab joined to a promising stability under physiological conditions suggest to propose this radioimmunoconjugate as a potential diagnostic radiopharmaceutical for β- radio-guided surgery.

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

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wendy Bernhard ◽  
Kris Barreto ◽  
Ayman El-Sayed ◽  
Carolina Gonzalez ◽  
Raja Solomon Viswas ◽  
...  
Keyword(s):  
Half Life ◽  
Growth Factor Receptor ◽  
Clinical Trial Application ◽  
Guided Surgery ◽  
Positron Emission ◽  
Infusion Reactions ◽  
Delayed Toxicity ◽  
Epidermal Growth ◽  
Pharmaceutical Properties ◽  
Formulation Stability

Abstract Background Epidermal 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. Methods Formulation 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. Results IRDye800CW-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. Conclusions Here, we show preclinical studies demonstrating that nimotuzumab conjugated to IRDye800CW is safe and does not exhibit toxicities commonly associated with EGFR targeting antibodies.

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