The development of humanized monoclonal antibodies (MAbs) with Lutetium-177 ([177Lu]Lu3+) has brought a paradigm shift in the arena of targeted therapy of various cancers. [177Lu]Lu-DOTA-Rituximab and [177Lu]Lu-DOTA-Trastuzumab have gained prominence due to their improved therapeutic efficacy in the treatment of lymphoma and breast cancer. The clinical dose formulation of these radiolabeled MAbs, using low specific activity [177Lu]LuCl3, requires extensive optimization of the radiolabeling protocol. The present study merits the development of a single protocol which has been optimized for conjugation of Rituximab and Trastuzumab with p-NCS-benzyl-DOTA and further radiolabeling these immunoconjugates (ICs) with low specific activity [177Lu]LuCl3. Herein, we report a consistent and reproducible protocol for clinical dose formulations of [177Lu]Lu-DOTA-Rituximab and [177Lu]Lu-DOTA-Trastuzumab (~9.25 GBq each, equivalent to ~2 patient doses) with radiochemical yield (RCY) between 84 and 86% and radiochemical purities (RCP) >99%. The in vitro stabilities of both these radioimmunoconjugates (RICs) were retained up to 120 h post-radiolabeling, upon storage with L-ascorbic acid as stabilizer (concentration: ~ 220-240 μg/37MBq) at -20 °C. The ready-to-use formulation of clinical doses[177Lu]Lu-DOTA-Rituximab and [177Lu]Lu-DOTA-Trastuzumab has been successfully achieved by employing a single optimized protocol. While [177Lu]Lu-DOTA-Rituximab has exhibited a high degree of localization in retroperitoneal nodal mass of refractory lymphoma patient, high uptake of [177Lu]Lu-DOTA-Trastuzumab has been observed in metastatic breast carcinoma patient with multiple skeletal metastases.
Keywords: Breast cancer; Clinical and pre-clinical study; Lu-177; Lymphoma; Radioimmunotherapy; Rituximab; Trastuzumab.
© 2023. The Author(s), under exclusive licence to World Molecular Imaging Society.