Y-90-DOTA-Nimotuzumab: Synthesis of a Promising beta(-) Radiopharmaceutical

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 beta(-) emitting radioimmunoconjugate (Y-90-DOTA-nimotuzumab) potentially useful to assess the feasibility of a new radio-guided surgery approach. Methods: The synthesis of Y-90-DOTA-nimotuzumab was performed in two days. Nimotuzumab was conjugated with a 50-fold excess of DOTA and then labelled with Y-90(3+). The Y-90-DOTA-nimotuzumab preparation was optimized considering several parameters such as pH, temperature and reaction volume. Moreover, the Y-90-DOTA-nimotuzumab stability was evaluated in human plasma. Results: The radioimmunoconjugate Y-90-DOTA-nimotuzumab was obtained with a radiochemical purity greater than 96%, and showed a good stability at 20 degrees C as well as at 37 degrees C in human plasma. Conclusions: The optimized conditions for a mild and easy preparation of Y-90-DOTA-nimotuzumab joined to a promising stability under physiological conditions suggest to propose this radioimmunoconjugate as a potential diagnostic radiopharmaceutical for beta(-) radio-guided surgery.