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

Background: Radioimmunotherapy is a feasible treatment modality for B-cell lymphomas expressing CD20 antigen. Tagging of anti-CD20 monoclonal antibody with a β(-) emitter will deliver radiation to the tumor preferentially, thereby causing its destruction. This work explores the utility of (177)Lu-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 (177)Lu. (177)Lu-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 (177)Lu-CHX-A"-DTPA-Rituximab was >95%. In the HPLC system, (177)Lu-CHX-A"-DTPA-Rituximab showed a single peak (Rt ∼15.5 minutes). In vitro cell binding studies showed 38.9%±1.1% binding of (177)Lu-CHX-A"-DTPA-Rituximab (∼6.7 nM of radioimmunoconjugate) with Raji cells which reduced to 17.7%±0.5% with the addition of 67 nM 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 (177)Lu-CHX-A"-DTPA-Rituximab toward CD20 antigen. It can be concluded that (177)Lu-CHX-A"-DTPA-Rituximab could be a promising agent in the treatment of NHL.