Concepts for design and analysis of receptor radiopharmaceuticals: The Receptor-Binding Radiotracers series of meetings provided the foundation.

A symposium at George Washington University on Receptor-Binding Radiotracers in 1980 and three follow-up meetings held at University of California, San Diego provided a forum for debating the critical concepts involved in the new field of designing and evaluating radiotracers for imaging receptors and transporters. This review is intended to educate young investigators who may be relatively new to receptor radiopharmaceutical development. Our anticipated audience includes researchers in basic pharmacology, radiochemistry, imaging technology and kinetic data analysis and how these disciplines have worked together to build our understanding of the human biology of transporters and receptor signaling in health and disease. We have chosen to focus on radiochemical design of a useful imaging agent and how design is coupled to analysis of data collected from dynamic imaging with that agent. Some pharmacology may be required for designing the imaging agent and some imaging physics may be important in optimizing the quality of data that is collected. However, the key to a successful imaging agent is matching the radiotracer to the target receptor and to analysis of the time-course data that is used to parse delivery from specific binding and subsequent metabolism or degradation. Properly designed imaging agents are providing critical information about human biology in health and disease as well as pharmacodynamic response to drug interventions. The review emphasizes some of the ideas that were controversial at the 1980 conference and chronicles with literature examples how they have resolved over the four decades of using radiotracers to study transporters and receptors in human subjects. These examples show that there are situations where a very small K