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06.09.2023 | Research Article

Intricacies in the Preparation of Patient Doses of [¹⁷⁷Lu]Lu-Rituximab and [¹⁷⁷Lu]Lu-Trastuzumab Using Low Specific Activity [¹⁷⁷Lu]LuCl₃: Methodological Aspects

verfasst von: Avik Chakraborty, Arpit Mitra, Sudeep Sahu, Megha Tawate, Sangita Lad, Kamaldeep, Sutapa Rakshit, Trupti Upadhye Bannore, Sujay Gaikwad, Geetanjali Dhotre, Mukti Kanta Ray, Archana Damle, Sandip Basu, Sharmila Banerjee

Erschienen in: Molecular Imaging and Biology | Ausgabe 1/2024

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Abstract

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.

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Titel: Intricacies in the Preparation of Patient Doses of [177Lu]Lu-Rituximab and [177Lu]Lu-Trastuzumab Using Low Specific Activity [177Lu]LuCl3: Methodological Aspects
verfasst von: Avik Chakraborty
Arpit Mitra
Sudeep Sahu
Megha Tawate
Sangita Lad
Kamaldeep
Sutapa Rakshit
Trupti Upadhye Bannore
Sujay Gaikwad
Geetanjali Dhotre
Mukti Kanta Ray
Archana Damle
Sandip Basu
Sharmila Banerjee
Publikationsdatum: 06.09.2023
Verlag: Springer International Publishing
Erschienen in: Molecular Imaging and Biology / Ausgabe 1/2024
Print ISSN: 1536-1632
Elektronische ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-023-01846-1

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Intricacies in the Preparation of Patient Doses of [¹⁷⁷Lu]Lu-Rituximab and [¹⁷⁷Lu]Lu-Trastuzumab Using Low Specific Activity [¹⁷⁷Lu]LuCl₃: Methodological Aspects

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