The physical chemistry of ligand-receptor binding identifies some limitations to the analysis of receptor images

The biophysical chemistry of ligand-receptor interactions imposes some rest rictions on the characteristics of a radioligand if it is to be a useful tr acer for accurately measuring the in vivo concentration of a specific cellu lar membrane receptor. This review discusses thermodynamic and kinetic late constant considerations in selecting a ligand for radiolabeling and imagin g. When radioligands of only modest specific activity are injected, one is able to use kinetic analysis to calculate the rate constant for the bimolec ular binding reaction as well as the receptor concentration. Images of regi onal receptor density can be constructed from analysis of emission imaging data when the binding occurs at a rate that is slower than the collision fr equency. A tracer that reacts with each collision cannot distinguish recept or density from blood flow. The theory of diffusion-limited reactions is re viewed and individual ligand-receptor examples are presented to demonstrate conditions where, even fur very fast forward reactions, the binding of rad ioligand to receptor is controlled by local biochemistry rather than by the purely physical process of diffusion. (C) 2001 Elsevier Science Inc. All r ights reserved.