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 Cy5TM (650-700nm) wavelengths are preferable to Cy3TM
(550-600nm) and Cy7TM (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