Radiolabeled muscarinic radioligands for in vivo studies

The biophysical chemistry of ligand-receptor interactions imposes some restrictions on the characteristics of a radioligand if it is to be a useful tracer for accurately measuring the in vivo concentration of a specific cellular membrane receptor. This review discusses thermodynamic and kinetic rate constant considerations in selecting a ligand for radiolabeling and imaging. When radioligands of only modest specific activity are injected, one is able to use kinetic analysis to calculate the rate constant for the bimolecular binding reaction as well as the receptor concentration. Images of regional receptor density can be constructed from analysis of emission imaging data when the binding occurs at a rate that is slower than the collision frequency. A tracer that reacts with each collision cannot distinguish receptor density from blood flow. The theory of diffusion-limited reactions is reviewed and individual ligandreceptor examples are presented to demonstrate conditions where, even for very fast forward reactions, the binding of radioligand to receptor is controlled by local biochemistry rather than by the purely physical process of diffusion.