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 177Lu-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 177Lu. 177Lu-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 177Lu-CHX-A”-DTPA-Rituximab was >95%. In the HPLC system, 177Lu-CHX-A”-DTPA-Rituximab showed a single peak (Rt ∼15.5 minutes). In vitro cell binding studies showed 38.9%±1.1% binding of 177Lu-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 177Lu-CHX-A”-DTPA-Rituximab toward CD20 antigen. It can be concluded that 177Lu-CHX-A”-DTPA-Rituximab could be a promising agent in the treatment of NHL.
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