PSMA-SPECIFIC ANTIBODY FRAGMENTS FOR PROSTATE CANCER IMAGING AND THERAPY

In this study we want to evaluate the potentiality of the use of a single chain Fv (scFv) for molecular imaging and therapy of Prostate Cancer. The target of this scFv is the Prostate Specific Membrane Antigen (PSMA), a type II transmembrane protein overexpressed in advances stages of this disease. In the past we have generated the murine antibody D2B recognizing hPSMA, whose diagnostic specificity has been investigated in xenograft murine models by imaging. In order to obtain a smaller protein able to better penetrate the tissues we decided to convert the murine monoclonal antibody D2B into a format like scFv. This format, due to its smaller size, have also the advantage, compare to the entire antibody, to have a faster clearance from the blood. The scFv has been constructed and its functionality has been tested with success on LNCaP cells. Using BIAcore (a technology able to measure the kinetic interaction between two molecules) we showed that the affinity of our scFv is still remarkable despite its monovalent binding. One goal of the present study is the assessment of potential role of this antibody fragment as diagnostic reagent for the development of radiopharmaceuticals for tumor characterization and molecular imaging. A second goal of the project is the production of a completely human antibody fragment against hPSMA in order to develop a reagent more suitable for therapy. We used phage display technology to convert the murine antibody in a human antibody applying guided selection technology which permits to generate an antibody with the specificity and functionality of the starting rodent mAb.