HER2/NEU GENE EXPRESSION PRODUCTS EVALUATED WITH SUPERPARAMAGNETIC, GENETICALLY ENGINEERED ANTIBODIES

Her2/neu is a protooncogene often amplified and overexpressed in ovary and breast cancer cells. HER2/neu receptors - HER2/neu gene expression products stimulate signal transduction pathways leading to increased cell proliferation. The level of its expression is associated with cancer malignancy. Therefore, HER2/neu is an important indicator of cancer malignancy, as well as, a target for antibody guided cancer therapies. The main objective of this work was to develop molecular probes, which would report levels of HER2/neu gene expression and anatomical distribution of its products in vivo. Magnetic resonance imaging (MRI) is particularly suitable for this endeavor, as it offers not only the best spatial resolution from all in vivo imaging modalities currently available, but also the topographic reference for location of these probes within anatomy of the human body. Superparamagnetic single chain variable fragment (scFv) antibodies targeting HER2/neu receptors were genetically engineered. They warranted high labeling specificity and affinity revealed with EDXSI, as well as, induced significant changes in relaxivity detected with NMR. This study demonstrated a proof of concept for using superparamagnetic scFvs in diagnostic evaluation of levels of gene expression products with NMR and MRI for planning receptor targeted therapies.