A review of graphical methods for tracer studies and strategies to reduce bias

Graphical techniques provide simple methods for the analysis of data from tracer studies. They provide considerable ease of computation compared to the optimization of individual model parameters in the solution of the differential equations generally used to describe the binding of tracers. The theoretical work of Patlak which was applied to irreversible tracers formed the basis for extensions of graphical techniques to reversibly binding tracers. The advantage of graphical methods is that they are not dependent upon a particular model structure but provide a measure of tracer binding that can be interpreted in terms of a model structure if desired. They provide a visual way to distinguish the type of binding whether reversible or irreversible in the initial studies of new ligands. Conditions under which the graphical techniques can be applied are considered as well as problems encountered with slow binding components. One problem in the use of these methods particularly the method for reversible tracers is the bias generated due to the presence of statistical noise. Some recently proposed techniques for reducing the noise are considered.