Often times ligands or receptors are over expressed in diseased tissues and can be utilized to image agents to these tissues via protein-ligand interactions. We have demonstrated that conjugation of imaging agents to natural ligands can generate useful imaging probes. These studies have also demonstrated the need to optimize conjugation strategies to retain the bio-activity of the conjugated ligands.
The rate and extent to which imaging agents are processed by a receptor will dictate the potential usefulness of a receptor as an imaging target. We have developed several high-throughput modalities to rapidly assess the utility of a particular receptor as an imaging target.
Electron microscopy is currently being used in collaboration with Dr. Peter J. Peters of the Netherlands Cancer Institute to investigate the intracellular accumulation and movement MR contrast agents. These studies are revealing the complicated way the cell processes imaging probes and this research will ultimately allow the design of more effective agents.
Amplification refers to imaging agents that change physicochemical properties upon specific interaction with targets resulting in increased signal. This can be due to activation of the probe by the target resulting in signal generation, for example an enzyme, or due to specific binding and acquisition of the probe resulting increased signal, for example receptor mediated internalization.