Theoretical relationships of receptor and delivery sensitivities and measurable parameters in in vivo neuroreceptor-radioligand interactions.
basic_science · Level V
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Abstract
In vivo quantification of neuroreceptors in human brains by PET or SPECT is complicated by the fact that a number of variables other than receptor concentration may influence the observed radioactivity in a brain region. This consideration has led the authors to formulate rigorous mathematical definitions of the concepts of receptor and delivery sensitivities. It has been speculated that a neuroreceptor-radioligand system having a high (low) receptor sensitivity would have a low (high) delivery sensitivity, and that the receptor sensitivity of a neuroreceptor-radioligand system can be determined by observing the time-course of the brain radioligand concentration following injection of no carrier added (nca) radioligand. Computer simulation studies of the characteristics of a simple model for in vivo neuroreceptor-radioligand interaction show that, under a set of realistic restrictions, there is a unique and intuitively satisfying relationship between receptor and delivery sensitivities: receptor sensitivity+delivery sensitivity approximately 1. In addition, the receptor sensitivity can be computed as a function of the observable parameters of the nca radioligand time course. These straightforward relationships are surprising in light of the complexity of the analytical solutions.