Accurate measurement of receptor concentration bmax and dissociation equilibrium constant KD with PET requires tissue measurements at different levels of receptor saturation and measurement of non-specific binding. Theoretically, this can be achieved with a single bolus injection of moderate specific activity (SA) ligand which will saturate a substantial fraction of available receptors. Typically, however, measurements are performed with high and low SA bolus injections. These studies require continuous scanning and blood sampling, and non-linear parameter estimation using an appropriate model. We have developed a more model-independent approach and applied it to the opiate antagonist 18F-(-)-cyclofoxy (CF). Previously, we developed a method for producing true equilibrium by a combination of bolus and continuous infusion of CF. In this way, the total tissue volume of distribution (representing free, non-specifically bound, and specifically bound tracer) can be determined directly from the concentration ratio of tissue to metabolite-corrected plasma. In this study, we extend this approach to produce equilibrium states at multiple specific activity levels of CF as well its inactive enantiomer (+)CF or a competitive inhibitor, naloxone. This data collection procedure allows a simple, direct calculation of Bmax and KD on a pixel by pixel basis and provides the basis for the application of this technique in humans. This study involves the development of study procedures and data analysis strategies, comparison of results with previous bolus studies, and application to various primate models including unilateral and bilateral MPTP-treated animals. The study is currently is in the phase of data analysis and manuscript preparation.
