Synthesis and Preclinical Evaluation of 177Lu-CHX-A"-DTPA-Rituximab as a Radioimmunotherapeutic Agent for Non-Hodgkin's Lymphoma

Introduction: Radioimmunotherapy is a feasible treatment modality for B-cell lymphomas expressing CD20 antigen. Tagging of anti-CD20 monoclonal antibody with a (-) emitter will deliver radiation to the tumor preferentially, thereby causing its destruction. This work explores the utility of Lu-177-CHX-A-DTPA-Rituximab as a radioimmunotherapeutic agent for non-Hodgkin's lymphoma (NHL). Methods: Rituximab was conjugated with p-NCS-Bn-CHX-A-DTPA and radiolabeled with Lu-177. Lu-177-CHX-A-DTPA-Rituximab was characterized by SE-HPLC. In vitro cell binding and inhibition studies were carried out in Raji cells which express CD20 antigen. Biodistribution studies were performed in SCID mice bearing lymphoma at various time intervals. Results: The CHX-A-DTPA-Rituximab conjugate prepared had three molecules of DTPA per Rituximab molecule. Radiochemical purity of Lu-177-CHX-A-DTPA-Rituximab was >95%. In the HPLC system, Lu-177-CHX-A-DTPA-Rituximab showed a single peak (R-t approximate to 15.5 minutes). In vitro cell binding studies showed 38.9%1.1% binding of Lu-177-CHX-A-DTPA-Rituximab (approximate to 6.7nM of radioimmunoconjugate) with Raji cells which reduced to 17.7%+/- 0.5% with the addition of 67nM of cold antibody. Biodistribution studies showed good tumor uptake at all the time points studied. Conclusions:In vitro and in vivo studies showed good specificity of Lu-177-CHX-A-DTPA-Rituximab toward CD20 antigen. It can be concluded that Lu-177-CHX-A-DTPA-Rituximab could be a promising agent in the treatment of NHL.