Preparation of clinical‐scale 177Lu‐Rituximab: Optimization of protocols for conjugation, radiolabeling, and freeze‐dried kit formulation. (23rd March 2017)

• Record Type: Journal Article
• Authors: Guleria, Mohini; Das, Tapas; Kumar, Chandan; Amirdhanayagam, Jeyachitra; Sarma, Haladhar D.; Banerjee, Sharmila
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 60:Number 5(2017)
• Page Start: 234
• Page End: 241
• Publication Date: 2017-03-23
• Subjects: freeze‐dried Rituximab kit -- radioimmunotherapy -- Rituximab -- 177Lu -- 177Lu‐Rituximab; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3493
• Languages: English
• ISSNs: 0362-4803

Abstract

Abstract : Rituximab is a monoclonal chimeric antibody, which has been approved by the US Food and Drug Administration for immunotherapy of non–Hodgkin lymphoma. Bexxar and Zevalin are the two other approved radiolabeled antibodies for radioimmunotherapy of non–Hodgkin lymphoma; however, they are of murine origin that reduces their treatment efficacy. So as to circumvent this, efforts have been made to radiolabel Rituximab with various therapeutic radioisotopes. In the present study, an effort has been made to optimize the conjugation (bifunctional chelating agent and antibody) and radiolabeling procedures for the preparation of clinical‐scale 177 Lu‐labeled Rituximab. An attempt was also made to prepare the freeze‐dried Rituximab kit for the easy and convenient clinical translation of the agent. Clinical‐scale 177 Lu‐Rituximab (40 mCi, 1.48 GBq) was prepared with >95% radiochemical purity using the kit. Biological evaluation of 177 Lu‐Rituximab was performed by in vitro cell binding studies in Raji cell lines, which showed satisfactory binding at 4°C and 37°C. Pharmacokinetic behavior of the agent, evaluated by biodistribution studies in normal Swiss mice, revealed high blood and liver uptake at the initial time points, although it exhibited slow and gradual clearance with time. The study indicates that clinical‐scale 177 Lu‐Rituximab could be conveniently formulated using the methodology described in the present article. Abstract : Methodology for the formulation of clinical‐scale 177 Lu‐Rituximab using the freeze‐dried Rituximab kit, developed in‐house, has been described. Biological efficacy of the radiolabeled agent has been studied by in vivo pharmacokinetic evaluation and in vitro cell binding studies.