Development of novel radiolabeled anti-CD20 antibody fragment for B-lymphocyte imaging in Non-Hodgkin's lymphoma patients Summary of research proposal

B-lymphocytes play an important role in pathogenesis of Non-Hodgkin's lymphoma (NHL). NHL must be characterized with certainty before therapy is initiated. Approx. 90% of B-lymphocyte expressed CD20, therefore particularly suitable target for immunoimaging. Although an anti-CD20 probe is required for in-vivo imaging of CD20 positive B-lymphocyte infiltration. Radiolabeled monoclonal antibody (mAb) offers possibility to target tumour antigens for immunoimaging. However, intact antibodies are large proteins (~150 kDa) with long invivo half-lives and low penetration into tumours. Prolonged residence time in blood and subsequently extensive radioactive exposure to normal organs can be toxic and lead to organ failure. To overcome the limitations of intact antibodies, we planned to produce smaller antibody fragments (Fab;~50 kDa). Due to their small size, these fragments may exhibit improved tumour penetration and rapid clearance from the blood; and allows radiolabelling with positron emitter isotopes, which will allow a high resolution Positron Emission Tomography (PET) imaging. Moreover, the innovative PET imaging technique is quantitative, non-invasive, and can therefore be repeated over time, to follow-up dosedependency and the time course of drug effects. Therefore, aim of this project is to develop and evaluate a new radiolabeled anti-CD20 Fab fragment for molecular imaging of tumour infiltrating CD20 positive B-lymphocytes.