Molecular targeting as a contrast agent mechanism for fluorescence endoscopy

Abstract

Several mechanisms of action can be employed for a molecular imaging contrast agent for use with endoscopy. Targeting of cell surface molecules that are up regulated at an early disease stage, with a fluorescent labelled vector is one attractive approach. However, it suffers from the inherent limitation that the concentration of agent available is fundamentally limited by the concentration of receptor molecules available. Simple models indicate that for successful imaging with a targeting approach, the imaging system should be able to adequately image concentrations in the nanomolar region. Such low reporter molecule concentrations have implications for the choice of contrast agent. Target tissue size and location, the tissue native fluorescence contribution, the brightness of the reporter molecule, and photobleaching thresholds are all factors which contribute to the choice of reporter. For endoscopic imaging of millimetre sized target tissue volumes close to the surface Cy5^TM (650-700nm) wavelengths are preferable to Cy3^TM (550-600nm) and Cy7^TM (750-800nm). We have constructed a system optimised for sensitivity by tailoring light delivery, collection, filtering and detection, in order to address the fundamental technical performance limits for endoscopic applications. It is demonstrated through imaging system calibration, phantom based measurement and animal imaging data that low nanomolar concentrations of Cy5 based fluorescent contrast agent in millimetre sized superficial lesions are adequately imaged with a clinically relevant endoscope system in real time. It is concluded that targeting is a technically viable approach for endoscopic applications.