Radiolabeling of anti-CD20 with 18F for imaging of CD20´s bio-distribution to predict response to rituximab therapy

Background: A standard way to image cell surface receptors such as CD20 is radiolabeling of their ligand and imaging bio-distribution by SPECT and PET which could be useful in diagnosis of a wide range of pathologies including rheumatoid arthritis (RA) and chronic lymphocytic leukemia (CLL). In vivo evaluation of CD20 enables clinicians to predict and quantify response to therapy. Anti-CD20 derivatives have been already labeled with 131I (Bexxar) and 90Y (Zevalin) in treating Non-Hodgkin s Lymphoma and 124I-rituximab PET/CT in patient with RA.Methods: Monoclonal antibody (mAb), either ofatumumab or obinutuzumab, would be labeled with 18F. Optimization of labeling can be achieved by varying parameters: antibody mass, reducing agent, 18F volume and activity. In vitro human plasma stability for 24 h at 37° would be investigated. Biodistribution study would be performed in BALB/C mice bearing lymphoma xenografts.Results: Acceptable radiolabeling yields could be achieved after reduction of antibody and long incubation time. Radiochemical purity could be performed by thin layer chromatography (TLC). Identification of product could be determined by high-performance liquid chromatography (HPLC). The tumor uptake of 18F-mAbs and biodistribution study in mice could be determined after imaging.Conclusion: Although use of zevalin and bexxar has come to end, need for CD20 imaging is yet a clinical demand. So, because of the particular construction of either Ofatumumab, a novel epitope on the CD20 antigen, or obinutuzumab, a novel glycolengineered type II mAb, are appropriate for labeling with 18F. We believe that 18F-mAbs could be clinically used in many CD20 disease to guide treatment.

کلیدواژه ها:

Cell surface receptors ، Anti-CD20 ، Monoclonal antibodies