Development of Targeted Molecular Imaging Agents
Dr. Sutcliffe’s research involves the design, synthesis and in vivo evaluation of targeted molecular imaging agents with a focus on PET. Her group has developed rapid radiolabeling technologies using both solid-phase and solution-phase chemistries to incorporate the short half-life PET radionuclide 18F into peptides. Peptide based radiopharmaceuticals are gaining extensive attention as targeted molecular imaging agents. It is therefore important that technologies are developed that allow these agents to be synthesized rapidly and screened both in vitro and in vivo to assess their efficacy. Her group applies radiolabeled peptides to target cell surface receptors in vivo using small animal imaging. Major cell surface receptors of interest include the integrin receptors alpha(v)beta(3) and alpha(v)beta(6). Integrins are cell surface glycoproteins involved in cell-cell and cell- extracellular matrix interactions. Their over expression has been associated with many diseases including cancer. In particular alpha(v)beta(6) is expressed at low or undetectable levels on normal tissue and is upregulated on many cancers including oral squamous cell carcinoma, breast cancer, pancreatic cancer and has recently been identified as a marker of prognosis in colon and lung cancer. In vivo imaging of this receptor could therefore have a significant impact on patient diagnosis, care and management. Dr Sutcliffe’s group uses two approaches to develop targeted molecular imaging agents to image cell surface receptors A “rational approach” based on known binding structures and a “random approach” using the one-bead-one-compound molecular library methodology. Peptides are synthesized using standard Fmoc chemistries, screened in vitro for affinity and selectivity and subsequently radiolabeled and screened in vivousing small animal imaging.
