Critical design issues in the targeted molecular imaging of cell surface receptors

The imaging of cell-surface receptors can be achieved using several methods, including single photon emission tomography (SPECT) positron emission tomography (PET), optical imaging and magnetic resonance imaging (MRI). The application of targeted MRI contrast agents is particularly well-suited to this task, provided that the agents reach the desired site efficiently and selectively. In addition, they should bind reversibly to the cell-surface receptor and give rise to a large change in cellular relaxation rate, in competition with binding to the natural substrate. Such approaches offer promise in the molecular imaging of neurotransmission in the brain, using conjugates that selectively target dopamine or glutamate receptor sub-types. Strategies based on the use of competitive antagonist vectors offer particular scope, as such conjugates are generally not taken into the target cell following cell surface receptor binding, in contrast to the use of MRI contrast agents based on agonists that tend to be internalised quickly or are designed to target intracellular sites.